%A Yang,Yong %A Richards,Jacob P. %A Gundrum,Jennifer %A Ojha,Anil K. %D 2018 %J Frontiers in Microbiology %C %F %G English %K mycobacteria,Biofilms,peroxide,Starvation,GlnR %Q %R 10.3389/fmicb.2018.01428 %W %L %M %P %7 %8 2018-July-04 %9 Original Research %# %! Peroxide resistance in mycobacterial biofilms %* %< %T GlnR Activation Induces Peroxide Resistance in Mycobacterial Biofilms %U https://www.frontiersin.org/articles/10.3389/fmicb.2018.01428 %V 9 %0 JOURNAL ARTICLE %@ 1664-302X %X Mycobacteria spontaneously form surface-associated multicellular communities, called biofilms, which display resistance to a wide range of exogenous stresses. A causal relationship between biofilm formation and emergence of stress resistance is not known. Here, we report that activation of a nitrogen starvation response regulator, GlnR, during the development of Mycobacterium smegmatis biofilms leads to peroxide resistance. The resistance arises from induction of a GlnR-dependent peroxide resistance (gpr) gene cluster comprising of 8 ORFs (MSMEG_0565-0572). Expression of gpr increases the NADPH to NADP ratio, suggesting that a reduced cytosolic environment of nitrogen-starved cells in biofilms contributes to peroxide resistance. Increased NADPH levels from gpr activity likely support the activity of enzymes involved in nitrogen assimilation, as suggested by a higher threshold of nitrogen supplement required by a gpr mutant to form biofilms. Together, our study uniquely interlinks a nutrient sensing mechanism with emergence of stress resistance during mycobacterial biofilm development. The gpr gene cluster is conserved in several mycobacteria that can cause nosocomial infections, offering a possible explanation for their resistance to peroxide-based sterilization of medical equipment.