OmpC-Dependent Bile Tolerance Contributes to E. coli Colonization of the Mammalian Intestine

Doranga, Sudhir; Conway, Tyrrell

doi:10.1128/spectrum.05241-22

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…Remarkably, closer inspection of the genes flanking the intergenic sequences represented in the concatenated targets revealed that certain functions were over-represented amongst the identified ITGR targets. Indeed, aside from the rcsDB locus, which acts as a master regulator for capsule biosynthesis ( 41 ), most of the flanking genes were involved primarily in antibiotic resistance, including: (i) yedS, within the previously identified yedR–yedS locus, which appears to mediate resistance against carbapenems ( 42 ); (ii) emrKY, within the emrKY–evgAS locus, which encodes for an efflux system that appears to be activate in response to tetracycline ( 43 ); (iii) evgAS , within the emrKY–evgAS locus, which encodes for a two-component regulatory system that controls the expression of several antibiotic resistance genes in E. coli ( 44 ); (iv) mdtABCD and baeSR , within the ibsB–(mdtABCD-baeSR ) locus, which appears to encode for a multidrug efflux pump and its corresponding two-component regulatory system, respectively ( 45 ); and (v) ompC , within the ompC–rcsDB locus, which encodes for an outer membrane porin implicated in resistance to various antibiotics ( 46 ) as well as bile salts required for successful colonization of the mammalian gut ( 47 ). Interestingly, these findings seem to mirror previous analyses that have identified ITGRs associated with antibiotic resistance genes as particularly informative for human and bovine E. coli strains ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Development of a logic regression-based approach for the discovery of host- and niche-informative biomarkers in Escherichia coli and their application for microbial source tracking

Yu,

Andersson-Li,

Maes

et al. 2024

Appl Environ Microbiol

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Microbial source tracking leverages a wide range of approaches designed to trace the origins of fecal contamination in aquatic environments. Although source tracking methods are typically employed within the laboratory setting, computational techniques can be leveraged to advance microbial source tracking methodology. Herein, we present a logic regression-based supervised learning approach for the discovery of source-informative genetic markers within intergenic regions across the Escherichia coli genome that can be used for source tracking. With just single intergenic loci, logic regression was able to identify highly source-specific (i.e., exceeding 97.00%) biomarkers for a wide range of host and niche sources, with sensitivities reaching as high as 30.00%–50.00% for certain source categories, including pig, sheep, mouse, and wastewater, depending on the specific intergenic locus analyzed. Restricting the source range to reflect the most prominent zoonotic sources of E. coli transmission (i.e., bovine, chicken, human, and pig) allowed for the generation of informative biomarkers for all host categories, with specificities of at least 90.00% and sensitivities between 12.50% and 70.00%, using the sequence data from key intergenic regions, including emrKY–evgAS , ibsB–(mdtABCD-baeSR), ompC–rcsDB, and yedS–yedR , that appear to be involved in antibiotic resistance. Remarkably, we were able to use this approach to classify 48 out of 113 river water E. coli isolates collected in Northwestern Sweden as either beaver, human, or reindeer in origin with a high degree of consensus—thus highlighting the potential of logic regression modeling as a novel approach for augmenting current source tracking efforts. IMPORTANCE The presence of microbial contaminants, particularly from fecal sources, within water poses a serious risk to public health. The health and economic burden of waterborne pathogens can be substantial—as such, the ability to detect and identify the sources of fecal contamination in environmental waters is crucial for the control of waterborne diseases. This can be accomplished through microbial source tracking, which involves the use of various laboratory techniques to trace the origins of microbial pollution in the environment. Building on current source tracking methodology, we describe a novel workflow that uses logic regression, a supervised machine learning method, to discover genetic markers in Escherichia coli , a common fecal indicator bacterium, that can be used for source tracking efforts. Importantly, our research provides an example of how the rise in prominence of machine learning algorithms can be applied to improve upon current microbial source tracking methodology.

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Section: Discussionmentioning

confidence: 99%

Development of a logic regression-based approach for the discovery of host- and niche-informative biomarkers in Escherichia coli and their application for microbial source tracking

Yu,

Andersson-Li,

Maes

et al. 2024

Appl Environ Microbiol

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“…Mouse colonization experiments were performed as described previously ( 49 , 73 , 76 – 79 ). Briefly, at least two sets of three CD-1 male mice (Charles River Laboratories, Wilmington, MA), aged 6–8 weeks, were acclimatized for 5 days, then transferred to individual cages and provided water containing streptomycin sulfate (5 g/L) for 24 h. Streptomycin sulfate selectively eliminates resident facultative anaerobes, which opens a niche for introduced E. coli .…”

Section: Methodsmentioning

confidence: 99%

“…Streptomycin-treated mice were colonized separately with E. coli MG1655 Str R Nal R wild type or E. coli MG1655 Str R ∆ glnG::cam , and on day 9 of colonization, when the mice were stably colonized, the mice were euthanized and total RNA was extracted from cecal mucus as previously described ( 79 ). Briefly, the cecal contents were squeezed out, and the lumen of the ceca was rinsed with Hanks salt solution (Thermo Scientific, catalog no.…”

Section: Methodsmentioning

confidence: 99%

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Nitrogen assimilation by E. coli in the mammalian intestine

Doranga,

Conway

2024

mBio

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Nitrogen is an essential element for all living organisms, including Escherichia coli . Potential nitrogen sources are abundant in the intestine, but knowledge of those used specifically by E. coli to colonize remains limited. Here, we sought to determine the specific nitrogen sources used by E. coli to colonize the streptomycin-treated mouse intestine. We began by investigating whether nitrogen is limiting in the intestine. The NtrBC two-component system upregulates approximately 100 genes in response to nitrogen limitation. We showed that NtrBC is crucial for E. coli colonization, although most genes of the NtrBC regulon are not induced, which indicates that nitrogen is not limiting in the intestine. RNA-seq identified upregulated genes in colonized E. coli involved in transport and catabolism of seven amino acids, dipeptides and tripeptides, purines, pyrimidines, urea, and ethanolamine. Competitive colonization experiments revealed that L-serine, N-acetylneuraminic acid, N-acetylglucosamine, and di- and tripeptides serve as nitrogen sources for E. coli in the intestine. Furthermore, the colonization defect of a L-serine deaminase mutant was rescued by excess nitrogen in the drinking water but not by an excess of carbon and energy, demonstrating that L-serine serves primarily as a nitrogen source. Similar rescue experiments showed that N-acetylneuraminic acid serves as both a carbon and nitrogen source. To a minor extent, aspartate and ammonia also serve as nitrogen sources. Overall, these findings demonstrate that E. coli utilizes multiple nitrogen sources for successful colonization of the mouse intestine, the most important of which is L-serine. IMPORTANCE While much is known about the carbon and energy sources that are used by E. coli to colonize the mammalian intestine, very little is known about the sources of nitrogen. Interrogation of colonized E. coli by RNA-seq revealed that nitrogen is not limiting, indicating an abundance of nitrogen sources in the intestine. Pathways for assimilation of nitrogen from several amino acids, dipeptides and tripeptides, purines, pyrimidines, urea, and ethanolamine were induced in mice. Competitive colonization assays confirmed that mutants lacking catabolic pathways for L-serine, N-acetylneuraminic acid, N-acetylglucosamine, and di- and tripeptides had colonization defects. Rescue experiments in mice showed that L-serine serves primarily as a nitrogen source, whereas N-acetylneuraminic acid provides both carbon and nitrogen. Of the many nitrogen assimilation mutants tested, the largest colonization defect was for an L-serine deaminase mutant, which demonstrates L-serine is the most important nitrogen source for colonized E. coli .

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Who is winning the war: Science or the adaptive molecular mechanisms of bacteria, evolving to survive antibiotic therapy?

Salazar,

Díaz,

Ferrara

2024

Gene Reports

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OmpC-Dependent Bile Tolerance Contributes to E. coli Colonization of the Mammalian Intestine

Abstract: Every mammalian intestine is colonized with Escherichia coli . Although E. coli is one of the most studied model organisms, how it colonizes the intestine is not fully understood.

Cited by 5 publications

References 69 publications

Development of a logic regression-based approach for the discovery of host- and niche-informative biomarkers in Escherichia coli and their application for microbial source tracking

Development of a logic regression-based approach for the discovery of host- and niche-informative biomarkers in Escherichia coli and their application for microbial source tracking

Nitrogen assimilation by E. coli in the mammalian intestine

Who is winning the war: Science or the adaptive molecular mechanisms of bacteria, evolving to survive antibiotic therapy?

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