Urinary tract infection drives genome instability in uropathogenic<i>Escherichia coli</i>and necessitates translesion synthesis DNA polymerase IV for virulence

Gawel, Damian; Seed, Patrick C.

doi:10.4161/viru.2.3.16143

Cited by 13 publications

(10 citation statements)

References 64 publications

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“…In these situations, the triggered SOS response is not only involved in DNA repair, but also influences antimicrobial resistance spread, general stress response and induction of virulence factors in organisms as uropathogenic E. coli , Salmonella enterica and Vibrio cholerae [10,49,50]. These mechanisms probably also occur in L. interrogans , and the full characterization of the DNA damage response is the first step to identify them.…”

Section: Discussionmentioning

confidence: 99%

Leptospira interrogans serovar Copenhageni Harbors Two lexA Genes Involved in SOS Response

et al. 2013

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Bacteria activate a regulatory network in response to the challenges imposed by DNA damage to genetic material, known as the SOS response. This system is regulated by the RecA recombinase and by the transcriptional repressor lexA. Leptospira interrogans is a pathogen capable of surviving in the environment for weeks, being exposed to a great variety of stress agents and yet retaining its ability to infect the host. This study aims to investigate the behavior of L. interrogans serovar Copenhageni after the stress induced by DNA damage. We show that L. interrogans serovar Copenhageni genome contains two genes encoding putative LexA proteins (lexA1 and lexA2) one of them being potentially acquired by lateral gene transfer. Both genes are induced after DNA damage, but the steady state levels of both LexA proteins drop, probably due to auto-proteolytic activity triggered in this condition. In addition, seven other genes were up-regulated following UV-C irradiation, recA, recN, dinP, and four genes encoding hypothetical proteins. This set of genes is potentially regulated by LexA1, as it showed binding to their promoter regions. All these regions contain degenerated sequences in relation to the previously described SOS box, TTTGN 5CAAA. On the other hand, LexA2 was able to bind to the palindrome TTGTAN 10TACAA, found in its own promoter region, but not in the others. Therefore, the L. interrogans serovar Copenhageni SOS regulon may be even more complex, as a result of LexA1 and LexA2 binding to divergent motifs. New possibilities for DNA damage response in Leptospira are expected, with potential influence in other biological responses such as virulence.

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Section: Discussionmentioning

confidence: 99%

Leptospira interrogans serovar Copenhageni Harbors Two lexA Genes Involved in SOS Response

et al. 2013

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“…The epithelial membrane also provides a physical barrier against the activity of phagocytes and antibody‐mediated clearance mechanisms. Within the epithelium, antimicrobial agents can damage UPEC, but UPEC survives through the induction of stress responses such as the DNA damage repair response (Justice et al ., ; Li et al ., ; Gawel & Seed, ).…”

Section: Intracellular Bacterial Communities (Ibcs): the Paradigm Of mentioning

confidence: 99%

Bacterial differentiation, development, and disease: mechanisms for survival

Justice

Harrison

Becknell

et al. 2014

FEMS Microbiol Lett

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Bacteria have the exquisite ability to maintain a precise diameter, cell length and shape. The dimensions of bacteria size and shape are a classical metric in the distinction of bacterial species. Much of what we know about the particular morphology of any given species is the result of investigations of planktonic cultures. As we explore deeper into the natural habitats of bacteria, it is increasingly clear that bacteria can alter their morphology in response to the environment in which they reside. Specific morphologies are also becoming recognized as advantageous for survival in hostile environments. This is of particular importance in the context of both colonization and infection in the host. There are multiple examples of bacterial pathogens that use morphological changes as a mechanism for evasion of host immune responses and continued persistence. This review will focus on two systems where specific morphological changes are essential for persistence in animal models of human disease. We will also offer insight into the mechanism underlying the morphological changes and how these morphotypes aid in persistence. Additional examples of morphological changes associated with survival will be presented.

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“…TLS is an important source of mutations that fuel bacterial evolution [ 8 – 13 ]. For several species of bacteria, deleting genes for TLS polymerases dramatically reduces rates of antibiotic resistance development in laboratory measurements, and in some cases even reduces infectivity [ 9 , 14 – 22 ]. Many of the drugs used to treat bacterial infections cause an increase in mutation rates as a result of TLS [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

DNA polymerase IV primarily operates outside of DNA replication forks in Escherichia coli

et al. 2018

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In Escherichia coli, damage to the chromosomal DNA induces the SOS response, setting in motion a series of different DNA repair and damage tolerance pathways. DNA polymerase IV (pol IV) is one of three specialised DNA polymerases called into action during the SOS response to help cells tolerate certain types of DNA damage. The canonical view in the field is that pol IV primarily acts at replisomes that have stalled on the damaged DNA template. However, the results of several studies indicate that pol IV also acts on other substrates, including single-stranded DNA gaps left behind replisomes that re-initiate replication downstream of a lesion, stalled transcription complexes and recombination intermediates. In this study, we use single-molecule time-lapse microscopy to directly visualize fluorescently labelled pol IV in live cells. We treat cells with the DNA-damaging antibiotic ciprofloxacin, Methylmethane sulfonate (MMS) or ultraviolet light and measure changes in pol IV concentrations and cellular locations through time. We observe that only 5–10% of foci induced by DNA damage form close to replisomes, suggesting that pol IV predominantly carries out non-replisomal functions. The minority of foci that do form close to replisomes exhibit a broad distribution of colocalisation distances, consistent with a significant proportion of pol IV molecules carrying out postreplicative TLS in gaps behind the replisome. Interestingly, the proportion of pol IV foci that form close to replisomes drops dramatically in the period 90–180 min after treatment, despite pol IV concentrations remaining relatively constant. In an SOS-constitutive mutant that expresses high levels of pol IV, few foci are observed in the absence of damage, indicating that within cells access of pol IV to DNA is dependent on the presence of damage, as opposed to concentration-driven competition for binding sites.

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Urinary tract infection drives genome instability in uropathogenicEscherichia coliand necessitates translesion synthesis DNA polymerase IV for virulence

Cited by 13 publications

References 64 publications

Leptospira interrogans serovar Copenhageni Harbors Two lexA Genes Involved in SOS Response

Leptospira interrogans serovar Copenhageni Harbors Two lexA Genes Involved in SOS Response

Bacterial differentiation, development, and disease: mechanisms for survival

DNA polymerase IV primarily operates outside of DNA replication forks in Escherichia coli

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