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        <title>Frontiers in Antibiotics | Antibiotic Development section | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/antibiotics/sections/antibiotic-development</link>
        <description>RSS Feed for Antibiotic Development section in the Frontiers in Antibiotics journal | New and Recent Articles</description>
        <language>en-us</language>
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        <pubDate>2026-05-13T20:11:22.977+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2026.1769369</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2026.1769369</link>
        <title><![CDATA[Antimycobacterial peptides as natural therapeutics for tuberculosis: mechanisms and structural features]]></title>
        <pubdate>2026-05-07T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Pulak Pritam</author><author>Sreelipta Das</author><author>Sandeep Kumar Behera</author><author>Monali Sahoo</author><author>Lopamudra Subudhi</author><author>Shibani Mohapatra</author><author>Alok Kumar Panda</author>
        <description><![CDATA[The disease tuberculosis, caused by Mycobacterium tuberculosis, is one of the leading causes of global human mortality. The rise of multidrug and extensively drug-resistant strains of the pathogen and the limited efficacy of the BCG vaccine is one of the major concerns worldwide. Conventional chemotherapy for tuberculosis is often very long and has several side effects. These factors lead to an urgent need for alternative, non-toxic therapeutic strategies with minimal side effects. Antimycobacterial peptides (AMPs), are a class of natural compounds that have shown a broad spectrum of anti-mycobacterial activity with a low propensity for the development of anti-mycobacterial resistance. This review summarizes the current antimycobacterial peptides, highlighting their structural features, physicochemical determinants, and their mechanism of action. Some of the key peptides have been critically discussed with respect to their membrane targeting mechanism. The role of structural modifications, such as disulfide bonding, cyclization, hydrophobicity tuning, and post-translational modifications, in enhancing antimycobacterial efficacy and stability is also examined. Consequently, the broad mechanism of action of these peptides and their role in the development of anti-tuberculosis drugs have been emphasized. This article combines mechanistic and structural insights to show how antimycobacterial peptides could become new anti-TB drugs. It also provides a guide for developing and improving peptide therapies for tuberculosis.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2026.1767602</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2026.1767602</link>
        <title><![CDATA[Microbial interactions of EDTA: recent advances and biological applications in the context of natural product modulation]]></title>
        <pubdate>2026-04-23T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Gunanidhi Sahoo</author><author>Aditi Jena</author><author>Sudipta Kumar Patra</author><author>Sujogya Kumar Panda</author><author>Satyanarayan Pal</author>
        <description><![CDATA[Background and objectivesEthylenediaminetetraacetic acid (EDTA) and its salts have been the choice of chelating agents since the 1940s. This review presents an updated details of their synthesis, general biology, ecotoxicological aspects, and applications as antimicrobial and antibacterial agents in combination with natural products.MethodsRelevant research papers were retrieved from PubMed, Web of Science, and Google Scholar through November 2025. Experimental uses of EDTA were excluded. The search terms used were “EDTA” AND “ECOTOXICOLOGY”; “EDTA” AND “GENOTOXICITY”; “EDTA” AND “ANTIMICROBIAL ACTIVITY”; “EDTA” AND “ANTIBACTERIAL ACTIVITY” AND “DENTAL” and “EDTA” AND “ANTICANCER ACTIVITY”, “EDTA IN COMBINATION WITH NATURAL PRODUCTS”.ResultsSodium/calcium salts of EDTA are water soluble, and their antiseptic efficacy is pH-dependent. They are effective against both Gram-positive and Gram-negative bacteria, as well as pathogenic yeasts, and adversely affect bacterial cell walls, thereby destabilizing biofilms. Multiple nature-derived compounds and standard antibiotics, in combination with EDTA and other therapeutic agents, minimize biofilms in intravascular and urinary catheters. It chelates various metal ions (including heavy metals) into a redox-inactive state, and thereby reduce their toxicity. Furthermore, it was shown to enhance the antimicrobial and antibacterial efficacy of various natural therapeutics when used together.Interpretation and conclusionsEDTA is a stable, readily available, affordable and comparatively safer chelating agent with antibacterial, antifungal, and antibiofilm properties. EDTA is now found to produce a synergistic effect when combined with natural therapeutics on their antimicrobial/antibiofilm activities. This approach proved fruitful in enhancing the capabilities of natural antibiotics against multidrug-resistant bacteria and in reducing the toxic effects of EDTA.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2026.1764314</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2026.1764314</link>
        <title><![CDATA[Traditional medicine and natural product based therapeutics in gingivitis management and microbial interactions]]></title>
        <pubdate>2026-04-06T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Pranita Rath</author><author>Sudipta Kumar Patra</author><author>Manisha Dash</author><author>Sandeep Kumar Behera</author><author>Shibani Mohapatra</author><author>Kabir Suman Dash</author><author>Alok Kumar Panda</author>
        <description><![CDATA[Gingivitis is a reversible inflammatory condition of gingival tissues and is majorly driven by the formation and accumulation of microbial biofilm. Untreated gingivitis often leads to periodontitis and ultimate tooth loss. The management of gingivitis through conventional methods relies mainly on the use of chemical antiseptics and antibiotics and the removal of plaque. However, the long-term use of the chemicals and antibiotics may alter the microflora and may also lead to antimicrobial resistance. This has led to increased interest in the usage of natural products-based herbal and traditional medicine as safer alternative medicine. This review provides a comprehensive overview of the pathogenesis of gingivitis with an emphasis on the microbial interaction and conversion of the microflora as the disease progresses. It evaluates the potential of major medicinal plants and their bioactive components used to cure the disease gingivitis. The antimicrobial, anti-inflammatory, antioxidant, and tissue-healing mechanisms of these medicinal plants are discussed alongside evidence from clinical trials. The review further highlights the limitations, such as the lack of standardized formulations and dosage variability differences among the various traditional and herbal medicinal practitioners, which prevents universal adoption of traditional medicine for treating gingivitis. In addition, advanced technologies such as the use of artificial intelligence for developing odontonutraceuticals, and next-generation polyherbal have also been explored. This review established the traditional and herbal medicine as an effective strategy for treating and managing gingivitis.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2026.1766594</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2026.1766594</link>
        <title><![CDATA[Antimicrobial peptides: emerging next-generation strategy for sustainable plant disease management]]></title>
        <pubdate>2026-03-25T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Dipayan Das</author><author>Tasqeen Khan</author><author>Jinkee Kalita</author><author>Sarvesh Rustagi</author><author>Sujogya Kumar Panda</author><author>Niraj Singh</author><author>Yugal Kishore Mohanta</author>
        <description><![CDATA[Plant diseases reduce agricultural productivity worldwide, and this decline is further accelerated by climate variability, monoculture cultivation systems, and the excessive use of synthetic agrochemicals. Overuse of chemical (synthetic) pesticides in agriculture results in ecological stress, including loss of beneficial microbes. As a solution, antimicrobial peptides (AMPs) are viable natural alternative to antibiotics and pesticides, due to their potent, broad-spectrum, and targeted properties, as well as their low susceptibility to the development of resistance. As small cationic amphipathic molecules found in plants, animals, and microorganisms, these AMPs are known to modulate membrane permeabilisation, disrupt intracellular systems, and stimulate the immune response. The AMP defence system depends on the highly interconnected gene network that supports efficient signal transmission and tightly coordinated gene clusters that support systematic responses to pathogen attack. These molecules can be considered as attractive biocidal agents due to their ability to target microbial membranes and cause rapid cell death, thereby having potential as broad-spectrum biocontrol agents against bacteria, fungi, and viruses. AMPs are also effective against multidrug-resistant pathogens. In plants, AMP families such as defensins, thionins, cyclotides, LTPs (lipid transfer proteins), snakins, and hevein-like peptides act as constitutive “natural antibiotics” which are involved in activating defensive signalling cascades upon pathogen infection. Microbial AMPs, such as bacteriocins, suppress pathogenic and spoilage bacteria by forming pores and inhibiting cell wall synthesis. At the same time, lipopeptides promote beneficial biofilms and plant defence pathways without direct toxicity. Progress in molecular biology, computational modelling, and synthetic biology has revealed the discovery, engineering, and optimisation of AMPs for agriculture. This review summarises the mechanisms of antibiotic mimicry by AMPs and discusses their structural and functional diversity, as well as their potential applications in sustainable plant disease management. The present study also evaluated AMPs as an alternative to chemical pesticides and antimicrobial agents, offering an environmentally compatible, durable, and efficient approach to preventing plant diseases.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2026.1768331</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2026.1768331</link>
        <title><![CDATA[Beyond antibiotics: the expanding horizon of microbial natural products]]></title>
        <pubdate>2026-02-26T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Suchitra Ku Panigrahy</author><author>Amrita kumari Panda</author><author>Aseem Kerketa</author><author>Rojita Mishra</author>
        <description><![CDATA[The continuous use of antibiotics has led to the development of antibiotic resistance among bacterial pathogens, posing a significant threat to both human and animal health. This necessitates exploring alternative solutions to combat this growing resistance. Natural products offer a viable alternative for microbial modulation, exhibiting diverse antibacterial processes and the capacity to modify microbial communities and biofilms. These compounds show potential as supplementary agents against resistant infections. Natural products derived from microbes are utilized as biofertilizers and biopesticides, enhancing crop yield and controlling plant pathogens, thereby offering an eco-friendly alternative to chemical fertilizers. Antimicrobial peptides (AMPs) are crucial for combating fish-associated pathogens, reducing mortality rates in the aquaculture industry. Various bacteriocins, are used as food preservatives to inhibit spoilage and pathogenic microorganisms proving their potential in the food industry. In this review, the potential role of natural products from microbes in the food, agriculture, and aquaculture industry sectors has been elucidated. The challenges and prospects were also discussed to provide a foundation for identifying new research opportunities.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2026.1767028</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2026.1767028</link>
        <title><![CDATA[Overcoming Candida biofilm resistance: targeting persister cells with probiotic-derived metabolites]]></title>
        <pubdate>2026-02-24T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Priyanka Debta</author><author>Binaya Krushna Sahu</author><author>Sudipta Kumar Patra</author><author>Fakir Mohan Debta</author><author>Ekagrata Mishra</author><author>Sujogya Kumar Panda</author>
        <description><![CDATA[Candida biofilms pose a significant complication in clinical settings due to antifungal drug tolerance and the presence of persister cells. Biofilm-mediated resistance is influenced by several associated factors, including the high density and extracellular matrix characteristics of the biofilm, metabolic downregulation, efflux pump activity, and stress-response signaling pathways, which ultimately diminish drug permeability and effectiveness. Within biofilms, persister cells form a small subpopulation of cells with unique phenotypic traits that enable them to survive lethal antifungal exposure and promote the recurrence of infection. Failure of antifungal treatments in eliminating biofilm and their resilient communities suggests a need for new, adjunct treatment options Recent findings have highlighted the therapeutic potential of probiotic-derived metabolites for inhibiting certain aspects of biofilm behavior and survival. These postbiotic compounds could offer a multi-faceted, low-toxicity treatment approach that may be used as an adjunct with existing antifungal therapies. Future investigations incorporating mechanistic studies, biofilm models, and drug product development for metabolite formulations could lead to a new treatment strategy for persistent Candida infections.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2026.1767032</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2026.1767032</link>
        <title><![CDATA[Natural product based approaches to overcome Candida glabrata and emerging AMR threats]]></title>
        <pubdate>2026-02-10T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Binaya Krushna Sahu</author><author>Sudipta Kumar Patra</author><author>Mahesh Chandra Sahu</author><author>Sujogya Kumar Panda</author>
        <description><![CDATA[The rise of C. glabrata as a serious, multidrug-resistant organism poses a significant and global challenge to the human health. The reasons C. glabrata has developed resistance to standard antifungal drugs, include the activation of efflux pumps, the production of biofilms, and changes in ergosterol biosynthesis. In light of the threat posed by C. glabrata, the potential of phytochemicals as therapeutic alternatives should be considered due to their diverse structures and ability to exhibit more than one type of antifungal activity. This review summarizes advances in the use of plant-based natural products displaying antifungal activity against C. glabrata, with an emphasis on key classes of phytochemicals, including flavonoids, terpenoids, phenolic compounds, alkaloids, and essential oils. While the proposed mechanisms include disruption of cell membranes, inhibition of ergosterol synthesis, attenuation of oxidative stress, and suppression of virulence and biofilm formation, it is important to note that most evidence arises from in vitro studies, with only limited mechanistic investigations on individual compounds. Although in vitro studies indicate promising antifungal and adjunctive effects, the available evidence remains largely preclinical, with variable synergistic outcomes. Such synergy not only enhances therapeutic efficacy but also reduces required drug dosages, thereby minimizing toxicity and delaying the emergence of resistance. Major limitations include inconsistency in phytochemical composition, insufficient pharmacokinetic data, and a lack of robust in vivo and clinical studies. This review critically integrates current knowledge, highlighting both the multi-target potential of phytochemicals against C. glabrata and the key challenges that must be addressed to enable realistic clinical translation. By prioritizing synergy-focused research, and methodological standardization, phytocompounds can be positioned not merely as standalone agents but as adjunctive modulators of antifungal resistance, paving the way for novel, effective, and sustainable therapeutic options against MDR C. glabrata.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2025.1692653</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2025.1692653</link>
        <title><![CDATA[Activity of Biocidin® against microbial biofilms]]></title>
        <pubdate>2026-01-28T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Amy V. Mundanchira</author><author>Agnes Wong</author><author>Kristen Klos-Maki</author><author>Jocelyn Strand</author><author>Cláudia N. H. Marques</author>
        <description><![CDATA[Biofilms—microbial communities—are present throughout the environment and interact with humans as part of the resident microbiome or when causing infection and disease. Antibiotics are commonly used to treat bacterial infections, including those due to biofilms. However, antimicrobial tolerance and resistance are common traits of these microbial communities. Resistance to antimicrobials is now widespread, and the search for alternative treatments, such as plant- or herbal-derived extracts, essential oils, and honey, is on the rise. Here, we investigated the effect of Biocidin®, a botanical supplement, on biofilms of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. A single (bolus) dose of Biocidin® resulted in a significant decrease (> 2 Log) of biofilm and planktonic populations, while a 24-h continuous dose of 25% and 50% Biocidin® led to a typical biphasic killing curve, with the latter concentration resulting in biofilm eradication of P. aeruginosa, S. aureus, and E. coli. Exposure to sub-inhibitory concentrations of Biocidin® did not affect biofilm viability. Results from this work have implications for the use of Biocidin® as a treatment for biofilm-associated infections and as a supplement in natural medicine.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2025.1562002</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2025.1562002</link>
        <title><![CDATA[Data transparency and reproducibility in health research: bridging the gap for early-career researchers]]></title>
        <pubdate>2025-04-29T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Sanjib Bhakta</author><author>Jianping Xie</author><author>Federico Pea</author><author>Stephen H. Gillespie</author>
        <description><![CDATA[In the evolving and interdisciplinary landscape of health and disease research, data transparency and reproducibility are increasingly recognised as essential for maintaining scientific integrity and trust. This article invites early-career researchers (ECRs) to engage critically with these principles while navigating the pressures of academic progression, publication demands, and career development. It examines the challenges ECRs face in maintaining reproducible practices and underscores the need for institutional support, inclusive training, and mentorship across all stages of the research career. Drawing on global initiatives and case studies, the article advocates for a more collaborative, diverse, and mentally healthy research culture. It also highlights alternative career pathways beyond academia, empowering ECRs to explore opportunities in industry, government, and non-governmental organisations. By integrating transparency with values such as team science, responsible metrics, and researcher wellbeing, this article reflects the ethos of the new generation of scientists and offers a timely call for systemic change and collective action to strengthen the future of research culture.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2024.1515874</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2024.1515874</link>
        <title><![CDATA[Analysis of engineered T7 bacteriophages containing genetic sequences encoding antimicrobial peptides]]></title>
        <pubdate>2025-01-15T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Tobias Ludwig</author><author>Daniela Volke</author><author>Andor Krizsan</author>
        <description><![CDATA[Because of the global spread of multi- and pan-resistant bacteria, there is a need to identify, research, and develop new strategies to combat these pathogens. In a previous proof-of-concept study, we presented an innovative strategy by genetically modifying lytic T7 bacteriophages. We integrated DNA fragments encoding for derivatives of the antimicrobial peptide (AMP) apidaecin into the phage genome to induce the production and release of apidaecin within the T7 infection cycle, thereby also targeting phage-resistant Escherichia coli bacteria. In this follow-up study, we optimized the apidaecin encoding insert to improve the expression of the apidaecin derivative Api805 by adding the secretion signal peptide of the OmpA protein. This prevented the detrimental effects of the peptide on the producing bacterial cell after its production. The integration of two copies of the OmpA-Api805 insert into the phage genome resulted in T7Select-2xOmpA-Api805 phages, which had a partially improved activity in inhibiting phage-resistant E. coli compared to the T7Select phages without insert and with only one copy of the OmpA-Api805 insert. Additionally, we showed that the combinatorial use of the lytic bacteriophage T7Select with the highly active and lytic AMPs CRAMP (cathelicidin-related AMP) and melittin against E. coli made the lysis process of the phage and the peptides more effective and prevented the growth of potentially AMP- and phage-resistant E. coli strains. The integration of DNA sequences derived from CRAMP and melittin into the phage genome resulted in the created T7Select-(M)CRAMP and T7Select-(M)melittin phages, which showed a lysis behavior like the phage without insert and partially inhibited the growth of potentially phage-resistant E. coli strains after the phage-mediated lysis.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2024.1399139</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2024.1399139</link>
        <title><![CDATA[Genomic modifications for enhanced antibiotic production in rifamycin derivative-producing Amycolatopsis mediterranei S699 strains: focusing on rifQ and rifO genes]]></title>
        <pubdate>2024-06-24T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Moritz Müller</author><author>Elena Bialas</author><author>Irina Sturm</author><author>Utkarsh Sood</author><author>Rup Lal</author><author>Andreas Bechthold</author>
        <description><![CDATA[Rifamycin and its derivatives are natural products that belong to the class of antibiotic-active polyketides and have significant therapeutic relevance within the therapy scheme of tuberculosis, a worldwide infectious disease caused by Mycobacterium tuberculosis. Improving the oral bioavailability of rifamycin B was achieved through semisynthetic modifications, leading to clinically effective derivatives such as rifampicin. Genetic manipulation of the rifamycin polyketide synthase gene cluster responsible for the production of rifamycin B in the Amycolatopsis mediterranei strain S699 represents a promising tool to generate new rifamycins. These new rifamycins have the potential to be further derivatized into new, ideally more effective, clinically usable compounds. However, the resulting genetically engineered strains only produce these new derivatives in low yields. One example is the strain DCO36, in which rifAT6 was replaced by rapAT2, resulting in the production of rifamycin B and the new derivative 24-desmethyl rifamycin B. Here we describe the successful method adaptation of the PCR-targeting Streptomyces gene replacement approach to Amycolatopsis mediterranei S699 and further on the implementation of genetic modifications that enable an increased production of the derivative 24-desmethyl rifamycin B in the mutant strain DCO36. The described genetic modifications resulted in a mutant strain of DCO36 with rifQ deletion showing a 62% increase in 24-desmethyl rifamycin B production, while a mutant with rifO overexpression showed a 27% increase.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2024.1362516</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2024.1362516</link>
        <title><![CDATA[Mycobactin analogue interacting with siderophore efflux-pump protein: insights from molecular dynamics simulations and whole-cell assays]]></title>
        <pubdate>2024-05-08T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Mousumi Shyam</author><author>Abhishek Thakur</author><author>Caroline Velez</author><author>Chris Daniel</author><author>Orlando Acevedo</author><author>Sanjib Bhakta</author><author>Venkatesan Jayaprakash</author>
        <description><![CDATA[IntroductionIn response to continued public health emergency of antimicrobial resistance (AMR), a significant key strategy is the discovery of novel mycobacterial efflux-pump inhibitors (EPIs) as potential adjuvants in combination drug therapy. Interest in identifying new chemotypes which could potentially synergize with the existing antibiotics and can be deployed as part of a combination therapy. This strategy could delay the emergence of resistance to existing antibiotics and increase their efficacy against resistant strains of mycobacterial species. In recent decades, notable approaches have been accounted for EPI development and have resulted in the discovery of several EPIs including SQ109 and AU1235. In context, to accelerate newer EPIs with novel mode of action here we have discussed mycobactin analogues and highlighted in silico binding orientation with siderophore efflux-pump proteins MmpL4/5.Methods3-(2-hydroxyphenyl)-5-(aryl)-pyrazoline series was investigated for whole-cell efflux-pump inhibitory activity against Mycobacterium smegmatis and Mycobacterium abscessus. Machine learning and molecular dynamics were performed to construct a MmpL4/5 complex embedded in a lipid bilayer to identify the putative binding site and to predict ligand-protein binding energetics. Furthermore, the identified HIT compound was investigated in synergistic assay with bedaquiline.ResultsCompound Il, 2-(5-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol, was identified as the most potent efflux pump inhibitor against M. smegmatis in whole-cell efflux-pump investigation. Followed HIT Il employed against M. abscessus for efflux-pump inhibition investigations and notable whole-cell efflux-pump inhibitory profile has been observed. The theoretical investigations predicted compound Il to be selective towards MmpL4, with significant hydrogen bonding and π-π stacking interactions effectively blocking a critical Asp-Tyr dyad interaction network necessary for proton translocation. Compound Il with bedaquiline highlighted an additive profile against the M. abscessus pathogen.ConclusionsMD simulations and whole-cell assays are indicating potential development of compound Il as an adjunct to the existing therapeutic regimen against mycobacterial infections.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2024.1384390</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2024.1384390</link>
        <title><![CDATA[Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli]]></title>
        <pubdate>2024-04-08T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Christopher Campion</author><author>Godefroid Charbon</author><author>Peter E. Nielsen</author><author>Anders Løbner-Olesen</author>
        <description><![CDATA[Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation. These anti-DnaA PNA-BPPs inhibited growth of wild-type Escherichia coli cells at low micromolar concentrations, and cells exposed to anti-DnaA PNA-BPPs exhibited characteristic hallmarks of chromosome replication inhibition. These results present one of very few compounds successfully targeting initiation of chromosome replication, an essential step in the bacterial cell cycle.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2023.1179354</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2023.1179354</link>
        <title><![CDATA[Gold complex compounds that inhibit drug-resistant Staphylococcus aureus by targeting thioredoxin reductase]]></title>
        <pubdate>2023-08-21T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Nagendran Tharmalingam</author><author>Shi Xu</author><author>Lewis Oscar Felix</author><author>Biswajit Roy</author><author>Ming Xian</author><author>Eleftherios Mylonakis</author><author>Beth Burgwyn Fuchs</author>
        <description><![CDATA[IntroductionThere is a significant need for new antimicrobial compounds that are effective against drug-resistant microbes. Thioredoxin reductase (TrxR) is critical in redox homeostasis and was identified as a potential drug target and confirmed through inhibition by compounds auranofin and Bay11-7085.MethodsAdditional TrxR inhibitors were designed and found to exhibit antimicrobial activity against Gram-positive (Enterococcus faecium and Staphylococcus aureus) and glutathione-deficient bacteria (Helicobacter pylori). Investigational compounds were tested for antimicrobial activity, anti-biofilm efficacy, target impact, and cytotoxicity.ResultsThe first-generation molecules AU1 and AU5 inhibited TrxR activity and inhibited methicillin-resistant S. aureus strain MW2 with minimal inhibitory concentrations (MIC) of 0.125 and 0.5 μg/mL, respectively. In an S. aureus enzymatic assay, AU1 inhibited TrxR enzymatic activity in a dose-dependent manner causing a decrease in intracellular free thiols. In addition, biofilm studies demonstrated that AU1 and AU5 reduced biofilm formation at 1X MIC and disrupted mature biofilms at 4X MIC. Cytotoxicity profiles were created using human cell lines and primary cells with LD50 exceeding MICs by at least 12X.DiscussionThus, AU1 and AU5 were TrxR inhibitors that yielded low-concentration antimicrobial activity impacting S. aureus in planktonic and biofilm forms with limited toxic liability.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2023.1162941</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2023.1162941</link>
        <title><![CDATA[Nanotherapeutic delivery of antibiotic cocktail enhances intra-macrophage killing of Mycobacterium marinum]]></title>
        <pubdate>2023-07-17T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Andrea M. Binnebose</author><author>Adam S. Mullis</author><author>Shannon L. Haughney</author><author>Balaji Narasimhan</author><author>Bryan H. Bellaire</author>
        <description><![CDATA[Mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in cold-blooded animals and is an opportunistic pathogen in humans. M. marinum is the closest genetic relative of the Mycobacterium tuberculosis complex and is a reliable surrogate for drug susceptibility testing. We synthesized and evaluated two nanoparticle (NP) formulations for compatibility with rifampicin, isoniazid, pyrazinamide, and ethambutol (PIRE), the front-line antimycobacterial drugs used in combination against active tuberculosis infections. Improved in vitro antimicrobial activity was observed with encapsulated rifampicin alone or in a cocktail of drugs formulated through co-encapsulation in amphiphilic polyanhydride NPs. Broth antimicrobial testing revealed that the encapsulation of PIRE in NP resulted in a significant increase in antimicrobial activity, with the benefit over soluble formulations at biologically relevant concentrations ranging from >10 to >3,000 fold. M. marinum-infected human macrophages treated with NP-PIRE were cleared of viable bacteria in 48 h following a single treatment, representing a >4 log reduction in colony-forming units and a >2,000-fold increase in antimicrobial activity. The amphiphilic polyanhydride nanoparticles demonstrated the ability to co-encapsulate PIRE antibiotics and enhance their antimicrobial activity against M. marinum in infected macrophages in culture and in vitro. These data suggest that polyanhydride nanoparticles are a promising nanotherapeutic for combatting Mycobacterium infections through improved intracellular targeting of encapsulated antibiotics.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2023.1122400</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2023.1122400</link>
        <title><![CDATA[Screening Amazon rainforest plant extracts for antimicrobial activity: a 15-year commitment to the Brazilian biodiversity]]></title>
        <pubdate>2023-07-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ivana Barbosa Suffredini</author><author>Jefferson de Souza Silva</author><author>Sergio Alexandre Frana</author><author>Katia Cristina Pinto</author><author>Keli Cristina Dias Bento</author><author>Erika Costa Rudiger</author><author>Paloma Kelly de Souza Belo</author><author>José Rodrigo de Arruda</author><author>Juliana Paola Schulze</author><author>Adriana Lígia de Castilho</author><author>Livia Roberta Piedade Camargo</author><author>Ricardo Olivieri Paulino</author><author>Yasmin de Oliveira Santos</author><author>Raphael Assis Leandro Morais</author><author>Karen Cristina Comin Maldonado</author><author>Gabriele Kolndorfer</author><author>Karolayne da Silva</author><author>Pietra Dantas de Jesus</author><author>Gabriella de Oliveira Moura</author><author>Victoria Rocha Brandão</author><author>Hevelton Araújo Ribeiro</author><author>Christian Henrique Komka Vara</author><author>Fabiane Massola</author><author>Ingrit Elida Collantes Díaz</author><author>Mateus Luís Barradas Paciencia</author><author>Selene Dall'Acqua Coutinho</author><author>Riad Naim Younes</author><author>Antonio Drauzio Varella</author>
        <description><![CDATA[IntroductionThe need for new tools to treat infections is constantly growing due to the possibilities of emerging diseases related to environmental changes, climatic catastrophes, microorganism resistance, and human and animal aging, leading to an evident unbalance in the planet’s health. Brazil contains the most significant portion of world biodiversity, a potential source of new antimicrobial natural products. Nonetheless, its environment, particularly its forests, and rainforests, is under threat, meaning that rapidly conducted, comprehensive research into the potential of antimicrobial activity to address this threat is urgently needed.MethodsIn this study, plants from the Amazon rainforest and the Atlantic forests were collected and tested against several pathogenic microbes relevant to humans, animals, and the environment, and subjected to large-scale susceptibility assays, bioautography, and Artemia salina toxicity assays. From the plants, 2,280 organic and aqueous extracts were obtained from different organs, namely leaves, barks, flowers, fruits, and seeds, and subjected to a large-scale susceptibility screening assay against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus mutans, Streptococcus sanguinis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Malassezia pachydermatis, Malassezia furfur, and Listeria monocytogenes. Results and discussionThe selected extracts were subjected to antimicrobial susceptibility tests to determine their inhibition zone diameters and minimum bactericidal concentrations, to bioautography, and to an Artemia salina toxicity assay, which resulted in 154 active extracts. Moreover, 111 out of 154 extracts were ranked based on scores established by the p-values and the mean rank differences in each set of test results. The final ranking identified which extracts should be studied in further phytochemical research using thin-layer chromatography techniques as a priority. The extracts obtained from plants belonging to Combretaceae, Connaraceae, Convolvulaceae, Fabaceae, Malpighiaceae, Moraceae, Piperaceae, Polygonaceae, and Salicaceae were selected as the most promising ones and used to support the identification of plant-based antimicrobial active compounds from the immense biodiversity of Brazilian forests.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2023.1101450</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2023.1101450</link>
        <title><![CDATA[Antimicrobial activity of a new class of synthetic retinoid antibiotics and comparator agents against ocular staphylococci]]></title>
        <pubdate>2023-03-22T00:00:00Z</pubdate>
        <category>Brief Research Report</category>
        <author>Camille André</author><author>Cassandra L. Schrank</author><author>Ana Victoria Cheng Jaramillo</author><author>Eleftherios Mylonakis</author><author>William M. Wuest</author><author>Michael S. Gilmore</author><author>Wooseong Kim</author><author>Paulo J. M. Bispo</author>
        <description><![CDATA[ObjectivesAntimicrobial resistance is global pandemic that poses a major threat to vision health as ocular pathogens, especially staphylococcal species, are becoming increasingly resistant to first-line therapies. Here we evaluated the antimicrobial activity of a new class of synthetic retinoids in comparison to currently used antibiotics against clinically relevant ocular staphylococcal isolates.MethodsAntimicrobial susceptibility testing was performed by broth microdilution for 3 novel synthetic retinoids (CD1530, CD437, and a CD437 analogue) and 7 comparator antibiotics, against a collection of 216 clinical isolates.ResultsCD437 MIC50 and MIC90 were 2 µg/mL for Staphylococcus aureus, and 1 µg/mL and 2 µg/mL respectively, for coagulase-negative staphylococci (CoNS). CD1530 (MIC50 = 2 µg/mL for all species) also displayed good activity with an in vitro potency slightly lower (2-fold) for S. aureus (MIC90 = 4 µg/mL) when compared to CD437. A CD437 analogue also demonstrated good in vitro activity (MIC50 = 2 µg/mL for all species) and potency (MIC90 = 2 µg/mL for MRSA and 4 µg/mL for MSSA and CoNS). In vitro potencies were similar or higher than that of comparator agents, and were not impacted by multidrug resistance phenotypes.ConclusionOur results demonstrate that synthetic retinoids display potent in vitro activity against ocular staphylococcal species, including multidrug-resistant isolates.]]></description>
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        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2023.1135485</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2023.1135485</link>
        <title><![CDATA[Repurposing inhibitors of phosphoinositide 3-kinase as adjuvant therapeutics for bacterial infections]]></title>
        <pubdate>2023-02-09T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Renee Fleeman</author>
        <description><![CDATA[The rise in antimicrobial resistance and the decline in new antibiotics has created a great need for novel approaches to treat drug resistant bacterial infections. Increasing the burden of antimicrobial resistance, bacterial virulence factors allow for survival within the host, where they can evade host killing and antimicrobial therapy within their intracellular niches. Repurposing host directed therapeutics has great potential for adjuvants to allow for more effective bacterial killing by the host and antimicrobials. To this end, phosphoinositide 3-kinase inhibitors are FDA approved for cancer therapy, but also have potential to eliminate intracellular survival of pathogens. This review describes the PI3K pathway and its potential as an adjuvant target to treat bacterial infections more effectively.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2023.1093156</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2023.1093156</link>
        <title><![CDATA[Resistance-resistant antibacterial treatment strategies]]></title>
        <pubdate>2023-01-30T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Jonathan I. Batchelder</author><author>Patricia J. Hare</author><author>Wendy W. K. Mok</author>
        <description><![CDATA[Antibiotic resistance is a major danger to public health that threatens to claim the lives of millions of people per year within the next few decades. Years of necessary administration and excessive application of antibiotics have selected for strains that are resistant to many of our currently available treatments. Due to the high costs and difficulty of developing new antibiotics, the emergence of resistant bacteria is outpacing the introduction of new drugs to fight them. To overcome this problem, many researchers are focusing on developing antibacterial therapeutic strategies that are “resistance-resistant”—regimens that slow or stall resistance development in the targeted pathogens. In this mini review, we outline major examples of novel resistance-resistant therapeutic strategies. We discuss the use of compounds that reduce mutagenesis and thereby decrease the likelihood of resistance emergence. Then, we examine the effectiveness of antibiotic cycling and evolutionary steering, in which a bacterial population is forced by one antibiotic toward susceptibility to another antibiotic. We also consider combination therapies that aim to sabotage defensive mechanisms and eliminate potentially resistant pathogens by combining two antibiotics or combining an antibiotic with other therapeutics, such as antibodies or phages. Finally, we highlight promising future directions in this field, including the potential of applying machine learning and personalized medicine to fight antibiotic resistance emergence and out-maneuver adaptive pathogens.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/frabi.2022.928365</guid>
        <link>https://www.frontiersin.org/articles/10.3389/frabi.2022.928365</link>
        <title><![CDATA[Implications of drug-induced phenotypical resistance: Is isoniazid radicalizing M. tuberculosis?]]></title>
        <pubdate>2022-09-09T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>RJH Hammond</author><author>Frank Kloprogge</author><author>O. Della Pasqua</author><author>Stephen H. Gillespie</author>
        <description><![CDATA[BackgroundTuberculosis treatment duration is long and does not guarantee eradication of infection. Shorter treatment regimens are a critical research objective to improve uptake and reduce the risk of relapse and bacterial resistance. The explanation for the need to continue treatment after patients are culture negative remains elusive. We have previously shown that the presence of lipid inclusions in mycobacterial cells is associated with an increase in antibiotic resistance.AimWe investigate the bactericidal effect of isoniazid and rifampicin on the expression of lipid inclusions and characterize the degree of the associated phenotypic antibiotic resistance to a range of anti-tuberculosis agents in current use.MethodsAntibiotic killing effect for both M. tuberculosis and M. komossense were investigated by both hollow fiber bioreactor (HFS) studies and static time kill curve (STKC) experiments. Following STKC cultures were stained with resazurin, Sytox green and Nile red to establish their live/dead (resazurin positive/Sytox positive) and lipid inclusion status, respectively. In addition, M. komossense was studied in the hollow fiber bioreactor model (HFS) and exposed to isoniazid (H) and rifampicin (R). The MIC of current antituberculosis agents for cells from the treated hollow fiber experiments were tested.ResultsAntibiotic killing was similar for both species. For M. komossense; isoniazid was ineffective at the established MIC (1 mg/L) in the hollow fiber bioreactor but rifampicin reduced the viable count rapidly at MIC (0.4 mg/L). When the two drugs were combined at their respective MICs the killing effect was significant and greater than separately. Cells exposed to isoniazid (1x and 9x MIC) for 168 h showed considerable numbers of recoverable viable cells when compared with a combination of 1x MIC R & H where there were no viable cells detectable. For both drugs the number of lipid body positive cells increased over time and this effect was most pronounced for isoniazid and was associated with phenotypic resistance to multiple anti-tuberculosis drugs.ConclusionOur results showed that isoniazid is a potent stimulator of lipid body accumulation, culture persistence, and phenotypic resistance to multiple anti-tuberculosis drugs. These findings emphasize the importance of understanding mechanisms of drug-drug interactions and phenotypic resistance in regimen building.]]></description>
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