Population-wide tolerance and persisters enable susceptible bacterial cells to endure hostile environments, including antimicrobial exposure. The SOS response can play a significant role in the ...generation of persister cells, population-wide tolerance, and shielding. The SOS pathway is an inducible DNA damage repair system that is also pivotal for bacterial adaptation, pathogenesis, and diversification. In addition to the two key SOS regulators, LexA and RecA, some other stressors and stress responses can control SOS factors. Bacteria are exposed to DNA-damaging agents and other environmental and intracellular factors, including cigarette smoke, that trigger the SOS response at a number of sites within the host. The
Escherichia coli
TisB/IstR module is as yet the only known SOS-regulated toxin–antitoxin module involved in persister formation. Nevertheless, the SOS response plays a key role in the formation of biofilms that are highly recalcitrant to antimicrobials and can be abundant in persisters. Furthermore, the dynamic biofilm environment generates DNA-damaging factors that trigger the SOS response within the biofilm, fueling bacterial adaptation and diversification. This review highlights the SOS response in relation to antimicrobial recalcitrance to antimicrobials in four clinically significant species,
Escherichia coli
,
Pseudomonas aeruginosa
,
Staphylococcus aureus
, and
Mycobacterium tuberculosis
.
Genomes of all organisms are persistently threatened by endogenous and exogenous assaults. Bacterial mechanisms of genome maintenance must provide protection throughout the physiologically distinct ...phases of the life cycle. Spore-forming bacteria must also maintain genome integrity within the dormant endospore. The nucleoid-associated proteins (NAPs) influence nucleoid organization and may alter DNA topology to protect DNA or to alter gene expression patterns. NAPs are characteristically multifunctional; nevertheless, Dps, HU and CbpA are most strongly associated with DNA protection. Archaea display great variety in genome organization and many inhabit extreme environments. As of yet, only MC1, an archaeal NAP, has been shown to protect DNA against thermal denaturation and radiolysis. ssDNA are intermediates in vital cellular processes, such as DNA replication and recombination. Single-stranded binding proteins (SSBs) prevent the formation of secondary structures but also protect the hypersensitive ssDNA against chemical and nuclease degradation. Ionizing radiation upregulates SSBs in the extremophile
.
Exogenous triggers include UV irradiation, chemicals or oxidative compounds, acids, organic mutagens, some antibiotics (e.g., fluoroquinolones such as ciprofloxacin), trimethoprim, BETA lactam, and ...physical stressors (such as high pressure) that provoke activity of the Mrr restriction endonuclease generating DNA double-strand breaks (DBSs) 2. ...in Vibrio cholerae additional non-genotoxic antibiotics have been shown to induce the SOS response, namely, aminoglycosides, tetracycline, and chloramphenicol 3. ...an increase in conjugation frequencies could transiently induce the SOS response throughout bacterial populations.\n Other examples of studied associations between bacteria and chronic inflammation are the linkage of chronic carriage of Salmonella enterica serovar Typhi with a higher risk of carcinoma of the gallbladder 22 and the linkage of colonization by Bacteriodes fragilis with colon cancer 23. In vitro, chronic exposure to CDT produced by Helicobacter hepaticus promoted induction of genome instability due to impaired activation of the DDR and cell cycle checkpoints--properties associated with tumor progression 34. ...colibactin has been shown to promote colorectal cancer.
Abstract
Morphologically similar microbial communities that often form on the walls of geographically distinct limestone caves have not yet been comparatively studied. Here, we analysed phylotype ...distribution in yellow microbial community samples obtained from the walls of distinct caves located in Spain, Czech Republic and Slovenia. To infer the level of similarity in microbial community membership, we analysed inserts of 474 16S rRNA gene clones and compared those using statistical tools. The results show that the microbial communities under investigation are composed solely of Bacteria. The obtained phylotypes formed three distinct groups of operational taxonomic units (OTUs). About 60% of obtained sequences formed three core OTUs common to all three sampling sites. These were affiliated with actinobacterial Pseudonocardinae (30–50% of sequences in individual sampling site libraries), but also with gammaproteobacterial Chromatiales (6–25%) and Xanthomonadales (0.5–2.0%). Another 7% of sequences were common to two sampling sites and formed eight OTUs, while the remaining 35% were site specific and corresponded mostly to OTUs containing single sequences. The same pattern was observed when these data were compared with sequence data available from similar studies. This comparison showed that distinct limestone caves support microbial communities composed mostly of phylotypes common to all sampling sites.
Escherichia coli strains frequently are isolated from skin and soft tissue infections (SSTI); however, their virulence potential has not yet been extensively studied. In the present study, we ...characterized 102 E. coli SSTI strains isolated mostly from surgical and traumatic wounds, foot ulcers, and decubitus. The strains were obtained from the Institute of Microbiology and Immunology, University of Ljubljana, Slovenia. Phylogenetic backgrounds, virulence factors (VFs), and antibiotic resistance profiles were determined. Correlations between VFs and phylogenetic groups were established and analyzed with regard to patient factors. Further, the associations of the three most prevalent antibiotic resistance patterns with virulence potential were analyzed. Our results showed that the majority of the studied strains (65%) belonged to the B2 phylogenetic group. The most prevalent VF was ompT (80%), while toxin genes cnf1 and hlyA were found with prevalences of 32 and 30%, respectively. None of the investigated bacterial characteristics were significantly associated with patient gender, age, type of infection, or immunodeficiency. The most prevalent antibiotic resistance pattern was resistance to ampicillin (46%), followed by resistance to tetracycline (25%) and fluoroquinolones (21%). Strains resistant to ciprofloxacin exhibited a significantly reduced prevalence of cnf1 (P < 0.05) and usp (P < 0.01). Our study revealed that E. coli isolates from SSTIs exhibit a remarkable virulence potential that is comparable to that of E. coli isolates from urinary tract infections and bacteremia.
The
PAI
is a small pathogenicity island encoding
for the uropathogenic specific protein (Usp), a genotoxin and three associated downstream
genes that protect the producer against its own toxin. ...Bioinformatic analysis revealed the presence of the PAI
also in publically available
and
subps.
genome sequences. PAI
is in all examined sequences integrated within the
chromosomal intergenic region. The focus of this work was identification of the
promoter and regulatory elements controlling its activity. We show that, in both
and
, the divergent TyrR regulated P3 promoter of the
gene, encoding an aromatic amino acid membrane transporter, drives
transcription while H-NS acts antagonistically repressing expression. Our results show that the horizontally acquired PAI
has integrated into the TyrR regulatory network and that environmental factors such as aromatic amino acids, temperature and urea induce
expression.
Escherichia coli is known to be an important uropathogenic agent. Several models were developed for investigating the uropathogensis of E. coli, including the recent biomimetic porcine urothelial in ...vitro model. The aim of this study was to assess the cytokine response of the cells of the biomimetic porcine urothelial model to different E. coli strains. The production of nine different cytokines in response to E. coli infection was evaluated using the commercial pre-configured immunoassay multiplex Cytokine & Chemokine 9-Plex Porcine ProcartaPlex™ Panel 1 kit. Our results showed that cells of the biomimetic porcine urothelial model reacted to the presence of all the employed different E. coli strains, albeit with some differences in levels and types of cytokines produced. Increased production of IL-10, IL-8, TNF-α, IL-1β, IL-4 and IL-12p40 was observed. Statistical analysis (Fisher’s exact test) revealed a correlation between the high fold change in the immune response and the presence of the cnf1 gene that encodes the cytotoxic necrotizing factor. Our results shed light on the cytokine response of normal urothelial cells to different E. coli strains and have the potential to fuel the search for understanding the mechanisms behind the different cytokine responses to different E. coli strains.
Cells employ specific and nonspecific mechanisms to protect their genome integrity against exogenous and endogenous factors. The clbS gene is part of the polyketide synthase machinery (pks genomic ...island) encoding colibactin, a genotoxin implicated in promoting colorectal cancer. The pks is found among the Enterobacteriaceae, in particular Escherichia coli strains of the B2 phylogenetic group. Several resistance mechanisms protect toxin producers against toxicity of their products. ClbS, a cyclopropane hydrolase, was shown to confer colibactin resistance by opening its electrophilic cyclopropane ring. Here we report that ClbS sustained viability and enabled growth also of E. coli expressing another genotoxin, the Usp nuclease. The recA::gfp reporter system showed that ClbS protects against Usp induced DNA damage. To elucidate the mechanism of ClbS mediated protection, we studied the DNA binding ability of the ClbS protein. We show that ClbS directly interacts with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), whereas ssDNA seems to be the preferred substrate. Thus, the ClbS DNA-binding characteristics may serve bacteria to protect their genomes against DNA degradation.
Bacteriocins are antimicrobial peptides generally active against bacteria closely related to the producer. Escherichia coli produces two types of bacteriocins, colicins and microcins. The in vitro ...efficacy of isolated colicins E1, E6, E7, K and M, was assessed against Escherichia coli strains from patients with bacteraemia of urinary tract origin. Colicin E7 was most effective, as only 13% of the tested strains were resistant. On the other hand, 32%, 33%, 43% and 53% of the tested strains exhibited resistance to colicins E6, K, M and E1. Moreover, the inhibitory activity of individual colicins E1, E6, E7, K and M and combinations of colicins K, M, E7 and E1, E6, E7, K, M were followed in liquid broth for 24 hours. Resistance against individual colicins developed after 9 hours of treatment. On the contrary, resistance development against the combined action of 5 colicins was not observed. One hundred and five E. coli strains from patients with bacteraemia were screened by PCR for the presence of 5 colicins and 7 microcins. Sixty-six percent of the strains encoded at least one bacteriocin, 43% one or more colicins, and 54% one or more microcins. Microcins were found to co-occur with toxins, siderophores, adhesins and with the Toll/Interleukin-1 receptor domain-containing protein involved in suppression of innate immunity, and were significantly more prevalent among strains from non-immunocompromised patients. In addition, microcins were highly prevalent among non-multidrug-resistant strains compared to multidrug-resistant strains. Our results indicate that microcins contribute to virulence of E. coli instigating bacteraemia of urinary tract origin.
Urinary tract infections can be severe, sometimes fatal, diseases whose etiological pathogens are predominantly uropathogenic strains of
(UPEC). To investigate the UPEC pathogenesis, several models ...have already been established with minor or major disadvantages. The aim was to develop a simple, fast, and inexpensive biomimetic in vitro model based on normal porcine urothelial (NPU) cells that are genetically and physiologically similar to human bladder urothelium and to perform basic studies of
pathogenicity. Initially, the model was tested using a set of control
strains and, subsequently, with human
strains isolated either from patients with urinary infections or from the feces of healthy individuals. A drop in viability of NPU cells was used as a measure of the pathogenicity of the individual strain tested. To visualize the subcellular events, transmission and scanning electron microscopy was performed. The strains were tested for the presence of different virulence-associated genes, phylogroup, type of core lipid, O-serotype, and type of lipopolysaccharide and a statistical analysis of possible correlations between strains' characteristics and the effect on the model was performed. Results showed that our model has the discriminatory power to distinguish pathogenic from non-pathogenic
strains, and to identify new, potentially pathogenic strains.
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