Affiliation:
1. Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Abstract
ABSTRACT
Staphylococcus aureus
is a major human pathogen that causes a variety of illnesses, ranging from minor skin and soft tissue infections to more severe systemic infections. Although the primary host immune response can typically clear bacterial infections,
S. aureus
is uniquely resistant to inflammation. For instance, our laboratory has determined that
S. aureus
is highly resistant to nitric oxide (NO⋅), an important component of the innate immune response that plays a role in both immunomodulatory and antibacterial processes. Additionally, NO⋅ and its derivatives can cause damage to
S. aureus
DNA, more specifically, deamination and/or oxidation of DNA bases; however, regulation and repair mechanisms of DNA in
S. aureus
are understudied. Thus, we hypothesize that several DNA repair mechanisms may account for the replication fidelity of
S. aureus
and may contribute to fitness in the presence of NO⋅. Here, we show the role of several DNA repair mechanisms in
S. aureus
. More specifically, we found that recombinational repair genes
recJ
,
recG
, and
polA
may play a role in the repair of NO⋅-induced replication fork collapses. We also show the role of the base excision repair pathway protein, MutY, in reducing NO⋅-mediated mutagenesis. Overall, our results suggest that NO⋅ leads to DNA damage, which subsequently induces the activity of several DNA repair pathways, contributing to the replication fidelity and fitness of
S. aureus
.
IMPORTANCE
Pathogenic bacteria must evolve various mechanisms in order to evade the host immune response that they are infecting. One aspect of the primary host immune response to an infection is the production of an inflammatory effector component, nitric oxide (NO⋅).
Staphylococcus aureus
has uniquely evolved a diverse array of strategies to circumvent the inhibitory activity of nitric oxide. One such mechanism by which
S. aureus
has evolved allows the pathogen to survive and maintain its genomic integrity in this environment. For instance, here, our results suggest that
S. aureus
employs several DNA repair pathways to ensure replicative fitness and fidelity under NO⋅ stress. Thus, our study presents evidence of an additional strategy that allows
S. aureus
to evade the cytotoxic effects of host NO⋅.
Funder
HHS | NIH | National Institute of Allergy and Infectious Diseases
Publisher
American Society for Microbiology