Abstract
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.
Highlights
Under most detergent-free in vitro conditions, mycobacterial species grow as surface-associated, three-dimensionally organized multicellular communities, called biofilms, which develop through dedicated genetic programs (Ojha et al, 2005, 2008; Weiss and Stallings, 2013; Gupta et al, 2015; Chuang et al, 2016; Yang et al, 2017; Clary et al, 2018)
In our earlier study we identified 61 genes induced during maturation of M. smegmatis biofilms to be GlnR-dependent (Jenkins et al, 2013; Yang et al, 2017)
Mycobacteria express and utilize dedicated genes to build stress resistant biofilms (Richards and Ojha, 2014), raising a possibility that genetic programs involved in adaptation of resident cells within the architecture, and those in stress resistance overlap with each other
Summary
Under most detergent-free in vitro conditions, mycobacterial species grow as surface-associated, three-dimensionally organized multicellular communities, called biofilms, which develop through dedicated genetic programs (Ojha et al, 2005, 2008; Weiss and Stallings, 2013; Gupta et al, 2015; Chuang et al, 2016; Yang et al, 2017; Clary et al, 2018). Mycobacterial biofilms harbor a sizable subpopulation of bacilli that can survive extreme conditions including exposure to antibiotics and antiseptics (Falkinham, 2007; Ojha et al, 2008; Rose et al, 2015; Yang et al, 2017; Clary et al, 2018). Biofilm growth of some mycobacterial species, including the pathogenic species M. canettii, fosters horizontal gene transfer
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
