AUTHOR=Yang Yong , Richards Jacob P. , Gundrum Jennifer , Ojha Anil K. 

TITLE=GlnR Activation Induces Peroxide Resistance in Mycobacterial Biofilms

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01428

DOI=10.3389/fmicb.2018.01428

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Mycobacterium smegmatis</italic> biofilms leads to peroxide resistance. The resistance arises from induction of a <underline>G</underline>lnR-dependent <underline>p</underline>eroxide <underline>r</underline>esistance (<italic>gpr</italic>) gene cluster comprising of 8 ORFs (MSMEG_0565-0572). Expression of <italic>gpr</italic> 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 <italic>gpr</italic> activity likely support the activity of enzymes involved in nitrogen assimilation, as suggested by a higher threshold of nitrogen supplement required by a <italic>gpr</italic> mutant to form biofilms. Together, our study uniquely interlinks a nutrient sensing mechanism with emergence of stress resistance during mycobacterial biofilm development. The <italic>gpr</italic> 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.</p>