The cad locus of Enterobacteriaceae: More than just lysine decarboxylation

Torres, Alfredo G.

doi:10.1016/j.anaerobe.2008.05.002

Cited by 28 publications

(20 citation statements)

References 56 publications

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“…Among these, CadA has been implicated as a negative regulator of EHEC adhesion to tissue culture cells and in colonization of the intestine in animal studies [19,54]. It has also been postulated that mutational inactivation or deletion of the cadBA locus in Enterobacteriaceae may be pathoadaptive, enhancing survival and pathogenic potential of bacteria within a host [55,56]. Downregulation of cadBA through bile exposure, as observed herein, may increase the pathogenic potential of O157:H7 cells once they enter the intestine where bile is present.…”

Section: Discussionmentioning

confidence: 99%

Bile Salts Affect Expression of Escherichia coli O157:H7 Genes for Virulence and Iron Acquisition, and Promote Growth under Iron Limiting Conditions

Hamner

McInnerney²,

Williamson³

et al. 2013

PLoS ONE

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Bile salts exhibit potent antibacterial properties, acting as detergents to disrupt cell membranes and as DNA-damaging agents. Although bacteria inhabiting the intestinal tract are able to resist bile’s antimicrobial effects, relatively little is known about how bile influences virulence of enteric pathogens. Escherichia coli O157:H7 is an important pathogen of humans, capable of causing severe diarrhea and more serious sequelae. In this study, the transcriptome response of E. coli O157:H7 to bile was determined. Bile exposure induced significant changes in mRNA levels of genes related to virulence potential, including a reduction of mRNA for the 41 genes making up the locus of enterocyte effacement (LEE) pathogenicity island. Bile treatment had an unusual effect on mRNA levels for the entire flagella-chemotaxis regulon, resulting in two- to four-fold increases in mRNA levels for genes associated with the flagella hook-basal body structure, but a two-fold decrease for “late” flagella genes associated with the flagella filament, stator motor, and chemotaxis. Bile salts also caused increased mRNA levels for seventeen genes associated with iron scavenging and metabolism, and counteracted the inhibitory effect of the iron chelating agent 2,2’-dipyridyl on growth of E. coli O157:H7. These findings suggest that E. coli O157:H7 may use bile as an environmental signal to adapt to changing conditions associated with the small intestine, including adaptation to an iron-scarce environment.

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Section: Discussionmentioning

confidence: 99%

Bile Salts Affect Expression of Escherichia coli O157:H7 Genes for Virulence and Iron Acquisition, and Promote Growth under Iron Limiting Conditions

Hamner

McInnerney²,

Williamson³

et al. 2013

PLoS ONE

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“…To withstand the extremely low pH of the stomach, these pathogens have evolved complex, acid-inducible survival strategies. Despite the beneficial role that the CadBAC lysine-dependent acid resistance system might have in the survival of enteric organisms in the intestine, cumulative evidence indicates that the absence of these genes, due to deletions or insertional mutagenesis, in some members of the family Enterobacteriaceae results in an enhancement of their virulence phenotype (31). For example, it is well documented that attenuation of virulence phenotypes in Shigella flexneri 2a has been linked to expression of LDC and, specifically, to the production of cadaverine (7,18,19).…”

Section: Discussionmentioning

confidence: 99%

CadA Negatively Regulates Escherichia coli O157:H7 Adherence and Intestinal Colonization

Vázquez-Juárez

Kuriakose²,

Rasko

et al. 2008

Infect Immun

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Adherence of pathogenicOne of these factors is CadA, a lysine decarboxylase, and this protein has been proposed to negatively regulate virulence in several enteric pathogens. In the case of EHEC strains, CadA modulates expression of the intimin, an outer membrane adhesin involved in pathogenesis. Here, we inactivated cadA in O157:H7 strain 86-24 to investigate the role of this gene in EHEC adhesion to tissue-cultured monolayers, global gene expression patterns, and colonization of the infant rabbit intestine. The cadA mutant did not possess lysine decarboxylation activity and was hyperadherent to tissue-cultured cells. Adherence of the cadA mutant was nearly twofold greater than that of the wild type, and the adherence phenotype was independent of pH, lysine, or cadaverine in the media. Additionally, complementation of the cadA defect reduced adherence back to wild-type levels, and it was found that the mutation affected the expression of the intimin protein. Disruption of the eae gene (intimin-encoding gene) in the cadA mutant significantly reduced its adherence to tissue-cultured cells. However, adherence of the cadA eae double mutant was greater than that of an 86-24 eae mutant, suggesting that the enhanced adherence of the cadA mutant is not entirely attributable to enhanced expression of intimin in this background. Gene array analysis revealed that the cadA mutation significantly altered EHEC gene expression patterns; expression of 1,332 genes was downregulated and that of 132 genes was upregulated in the mutant compared to the wild-type strain. Interestingly, the gene expression variation shows an EHEC-biased gene alteration including intergenic regions. Two putative adhesins, flagella and F9 fimbria, were upregulated in the cadA mutant, suggestive of their association with adherence in the absence of the Cad regulatory mechanism. In the infant rabbit model, the cadA mutant outcompeted the wild-type strain in the ileum but not in the cecum or mid-colon, raising the possibility that CadA negatively regulates EHEC pathogenicity in a tissue-specific fashion.

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“…Such beneficial mutations have been described for diverse bacteria, including E. coli, for improved nutrient scavenging, increased resistance to stresses or antibiotics (15)(16)(17)(18), and enhanced pathogenicity in bacterial pathogens, a phenomenon also known as patho-adaptation (19,20). Classical examples of patho-adaptation include the genes encoding lysine decarboxylase (20)(21)(22)(23)(24), type I fimbrial adhesin (25)(26)(27)(28)(29), and the curli fimbriae (29). Loss-of-function mutations in genes encoding the global transcriptional regulators RpoS and RcsB were reported for the STEC population, generating variants with distinct physiological properties, such as the expression of virulence genes, biofilm formation, stress resistances, and catabolic potential (30,31).…”

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confidence: 99%

An Environmental Shiga Toxin-Producing Escherichia coli O145 Clonal Population Exhibits High-Level Phenotypic Variation That Includes Virulence Traits

Carter

Quiñones

et al. 2016

Appl Environ Microbiol

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b Shiga toxin-producing Escherichia coli (STEC) serotype O145 is one of the major non-O157 serotypes associated with severe human disease. Here we examined the genetic diversity, population structure, virulence potential, and antimicrobial resistance profiles of environmental O145 strains recovered from a major produce production region in California. Multilocus sequence typing analyses revealed that sequence type 78 (ST-78), a common ST in clinical strains, was the predominant genotype among the environmental strains. Similarly, all California environmental strains belonged to H28, a common H serotype in clinical strains. Although most environmental strains carried an intact fliC gene, only one strain retained swimming motility. Diverse stx subtypes were identified, including stx 1a , stx 2a , stx 2c , and stx 2e . Although no correlation was detected between the stx genotype and Stx1 production, high Stx2 production was detected mainly in strains carrying stx 2a only and was correlated positively with the cytotoxicity of Shiga toxin. All environmental strains were capable of producing enterohemolysin, whereas only 10 strains were positive for anaerobic hemolytic activity. Multidrug resistance appeared to be common, as nearly half of the tested O145 strains displayed resistance to at least two different classes of antibiotics. The core virulence determinants of enterohemorrhagic E. coli were conserved in the environmental STEC O145 strains; however, there was large variation in the expression of virulence traits among the strains that were highly related genotypically, implying a trend of clonal divergence. Several cattle isolates exhibited key virulence traits comparable to those of the STEC O145 outbreak strains, emphasizing the emergence of hypervirulent strains in agricultural environments.

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The cad locus of Enterobacteriaceae: More than just lysine decarboxylation

Cited by 28 publications

References 56 publications

Bile Salts Affect Expression of Escherichia coli O157:H7 Genes for Virulence and Iron Acquisition, and Promote Growth under Iron Limiting Conditions

Bile Salts Affect Expression of Escherichia coli O157:H7 Genes for Virulence and Iron Acquisition, and Promote Growth under Iron Limiting Conditions

CadA Negatively Regulates Escherichia coli O157:H7 Adherence and Intestinal Colonization

An Environmental Shiga Toxin-Producing Escherichia coli O145 Clonal Population Exhibits High-Level Phenotypic Variation That Includes Virulence Traits

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