Repair of DNA Damage Induced by Bile Salts in <i>Salmonella enterica</i>

Prieto, Ana I.; Ramos‐Morales, Francisco; Casadesús, Josep

doi:10.1534/genetics.106.060889

Cited by 109 publications

(135 citation statements)

References 86 publications

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“…Previous studies had shown that exposure of S. enterica to bile salts induces the SOS response (39,40). To investigate whether suppression of bile sensitivity by asmA mutations was accompanied by reduced bile-induced DNA damage, induction of the SOS system was monitored using a cea::lacZ fusion carried on pGE108 (47).…”

Section: Resultsmentioning

confidence: 99%

“…The mechanisms employed by Escherichia coli and Salmonella enterica to survive in the presence of bile are diverse and only partially understood (18) and involve a variety of cell functions: envelope structures that provide physical barriers to bile salts (31,45,55), efflux pumps that transport bile salts outside the cell (34,38,46,52), and DNA repair functions that maintain genome integrity (39,40). Resistance to bile is especially relevant in Salmonella physiology, since systemic infection leads to colonization of the hepatobiliary tract (35), where the concentration of bile is high and steady (23).…”

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confidence: 99%

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Roles of the Outer Membrane Protein AsmA of Salmonella enterica in the Control of marRAB Expression and Invasion of Epithelial Cells

et al. 2009

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A genetic screen for suppressors of bile sensitivity in DNA adenine methylase (dam) mutants of Salmonella enterica serovar Typhimurium yielded insertions in an uncharacterized locus homologous to the Escherichia coli asmA gene. Disruption of asmA suppressed bile sensitivity also in phoP and wec mutants of S. enterica and increased the MIC of sodium deoxycholate for the parental strain ATCC 14028. Increased levels of marA mRNA were found in asmA, asmA dam, asmA phoP, and asmA wec strains of S. enterica, suggesting that lack of AsmA activates expression of the marRAB operon. Hence, asmA mutations may enhance bile resistance by inducing gene expression changes in the marRAB-controlled Mar regulon. In silico analysis of AsmA structure predicted the existence of one transmembrane domain. Biochemical analysis of subcellular fractions revealed that the asmA gene of S. enterica encodes a protein of ϳ70 kDa located in the outer membrane. Because AsmA is unrelated to known transport and/or efflux systems, we propose that activation of marRAB in asmA mutants may be a consequence of envelope reorganization. Competitive infection of BALB/c mice with asmA ؉ and asmA isogenic strains indicated that lack of AsmA attenuates Salmonella virulence by the oral route but not by the intraperitoneal route. Furthermore, asmA mutants showed a reduced ability to invade epithelial cells in vitro.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Roles of the Outer Membrane Protein AsmA of Salmonella enterica in the Control of marRAB Expression and Invasion of Epithelial Cells

et al. 2009

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“…These facts could explain why RpoS does not affect mutagenesis in LT2. In contrast, a pathogenic S. enterica strain, expected to express RpoS normally (42,43), displayed DSB repairprotein DinB-, SOS-, and RpoS-dependent SIM when exposed to bile (a stressor) and induced bile-resistant mutants (46,47). Thus, use of DSB repair-protein-RpoS-, SOS-, and DinB-dependent mutation appears to occur in Salmonella but, as expected, to be confined to strains with functional RpoS.…”

Section: Dsb-dependent Stress-induced Mutagenesis In Wild-type Strainmentioning

confidence: 99%

Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in Escherichia coli

Shee

Gibson

Darrow

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

122

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Basic ideas about the constancy and randomness of mutagenesis that drives evolution were challenged by the discovery of mutation pathways activated by stress responses. These pathways could promote evolution specifically when cells are maladapted to their environment (i.e., are stressed). However, the clearest example-a general stress-response-controlled switch to errorprone DNA break (double-strand break, DSB) repair-was suggested to be peculiar to an Escherichia coli F′ conjugative plasmid, not generally significant, and to occur by an alternative stress-independent mechanism. Moreover, mechanisms of spontaneous mutation in E. coli remain obscure. First, we demonstrate that this same mechanism occurs in chromosomes of starving F − E. coli. I-SceI endonuclease-induced chromosomal DSBs increase mutation 50-fold, dependent upon general/starvation-and DNA-damage-stress responses, DinB error-prone DNA polymerase, and DSB-repair proteins. Second, DSB repair is also mutagenic if the RpoS generalstress-response activator is expressed in unstressed cells, illustrating a stress-response-controlled switch to mutagenic repair. Third, DSB survival is not improved by RpoS or DinB, indicating that mutagenesis is not an inescapable byproduct of repair. Importantly, fourth, fully half of spontaneous frame-shift and base-substitution mutation during starvation also requires the same stress-response, DSB-repair, and DinB proteins. These data indicate that DSB-repairdependent stress-induced mutation, driven by spontaneous DNA breaks, is a pathway that cells usually use and a major source of spontaneous mutation. These data also rule out major alternative models for the mechanism. Mechanisms that couple mutagenesis to stress responses can allow cells to evolve rapidly and responsively to their environment.antibiotic resistance | cancer | genome evolution | rapid evolution | stressinduced mutagenesis H ow, when, and where mutations form underpins understanding pathogen-host interactions, antibiotic resistance, aging, cancer progression and therapy resistance, and evolution generally. Initial models of mutagenesis that drives evolution imagined random stochastic processes, roughly constant with time, and blind to selective environments (1). In contrast, bacterial, yeast, and human cells appear to possess mechanisms that induce mutation pathways specifically during stress, under the control of stress responses (2) (stress-induced mutagenesis or SIM). These pathways suggest mechanisms by which genetic diversity could be generated preferentially when cells are maladapted to their environment (i.e., are stressed), potentially accelerating evolution responsively to environments, a major departure from classic views (1). However, the significance of such mechanisms has been debated, as have the mechanisms themselves.First, mutagenesis associated with the DNA-damage response has been argued to be an unavoidable consequence of induced DNA repair (3, 4), not an evolutionary engine (5, 6). Second, the strongest support for the idea of increas...

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“…bacterial cell membranes due to the detergent activity of bile acids (Begley et al, 2005), causes DNA damage (Prieto et al, 2004(Prieto et al, , 2006 and alters the conformation of proteins. Salmonella, however, resists bile through different mechanisms.…”

Section: Bilementioning

confidence: 99%

“…The genes encoding these proteins are regulated by the transcriptional regulator RamA, which is synthesized in response to bile (Baucheron et al, 2014). In addition, bile-induced DNA damages can be repaired by Dam-directed mismatch repair and by base excision repair, and the impairment of DNA replication rescued by SOS-dependent translation DNA replication and RecBCD-dependent recombinational repair (Prieto et al, 2006). Finally, Salmonella is also able to adapt to grow in extremely high bile concentrations if previously exposed to sublethal doses.…”

Section: Bilementioning

confidence: 99%