Escherichia coli ST58 has recently emerged as a globally disseminated uropathogen that often progresses to sepsis. Unlike most pandemic extra-intestinal pathogenic E. coli (ExPEC), which belong to ...pathogenic phylogroup B2, ST58 belongs to the environmental/commensal phylogroup B1. Here, we present a pan-genomic analysis of a global collection of 752 ST58 isolates from diverse sources. We identify a large ST58 sub-lineage characterized by near ubiquitous carriage of ColV plasmids, which carry genes encoding virulence factors, and by a distinct accessory genome including genes typical of the Yersiniabactin High Pathogenicity Island. This sub-lineage includes three-quarters of all ExPEC sequences in our study and has a broad host range, although poultry and porcine sources predominate. By contrast, strains isolated from cattle often lack ColV plasmids. Our data indicate that ColV plasmid acquisition contributed to the divergence of the major ST58 sub-lineage, and different sub-lineages inhabit poultry, swine and cattle.
segregates into phylogenetic groups, with group B2 containing both extraintestinal pathogenic
(ExPEC) and enteropathogenic
(EPEC) strains. Ten main B2 subgroups (subgroups I to X)/sequence type ...complexes (STcs), as well as EPEC lineages, have been identified. In the current study, we characterized ExPEC and EPEC strains of
B2 phylogenetic subgroups/STcs that colonize Swedish and Pakistani infants. Gut commensal
B2 strains, 120 from Swedish infants (
= 87) and 19 from Pakistani infants (
= 12), were assigned to B2 subgroups. Carriage of the bundle-forming pili and intimin adhesin was examined in the EPEC lineages. The ExPEC virulence markers and the time of persistence of the strains in the microbiota were previously determined. In total, 84% of the Swedish strains and 47% of the Pakistani strains belonged to 1 of the 10 main B2 subgroups (
= 0.001). Among the Swedish strains, the most common B2 subgroups were IX/STc95 (19%), II/STc73 (17%), VI/STc12 (13%), and III/STc127 (11%), with each subgroup carrying distinctive sets of ExPEC virulence markers. EPEC lineages with few ExPEC features constituted 47% of the Pakistani B2 strains but only 7% of the Swedish B2 strains (
= 0.0001). The subgroup distribution within phylogenetic group B2 strains colonizing the gut differed between Swedish and Pakistani infants. B2 subgroups with uropathogenic characteristics dominated the gut microbiota of Swedish infants, while EPEC lineage 1 strains frequently colonized the intestines of Pakistani infants. Moreover, within the B2 subgroups, ExPEC virulence genes were more prevalent in Swedish strains than in Pakistani strains. Thus, ExPEC traits exemplify the intestinal B2 strains from Western populations.
The intestinal microbiota is an important reservoir for bacteria that cause extraintestinal infections.
is found ubiquitously in the gut microbiota, and it also causes urinary tract infections, infantile septicemia, and meningitis. Urinary tract infections are usually caused by
strains that originate in the intestinal microbiota.
also causes gastrointestinal infections and is a major cause of diarrhea in infants worldwide. The abilities of certain
strains to cause infections are attributed to their virulence factors, i.e., bacterial components that contribute to the development of different diseases. Our study shows that different subtypes of potentially pathogenic
strains dominate in the gut microbiota of infants in different geographical areas and expands our knowledge of the interplay between bacterial commensalism and pathogenicity.
Staphylococcus aureus can colonize both the anterior nares and the gastrointestinal tract. However, colonization at these sites in the same individuals has not been studied, and the traits that ...facilitate colonization and persistence at these sites have not been compared. Samples from the nostrils and feces collected on 9 occasions from 3 days to 3 years of age in 65 infants were cultured; 54 samples yielded S. aureus. The numbers of nasal and fecal S. aureus strains increased rapidly during the first weeks and were similar at 1 month of age (>40% of infants colonized). Thereafter, nasal carriage declined, while fecal carriage remained high during the first year of life. Individual strains were identified, and their colonization patterns were related to their carriage of genes encoding adhesins and superantigenic toxins. Strains retrieved from both the nose and gut (
= 44) of an infant were 4.5 times more likely to colonize long term (≥3 weeks at both sites) than strains found only in the rectum/feces (
= 56) or only in the nose (
= 32) (
≤ 0.001). Gut colonization was significantly associated with carriage of the
gene, and long-term colonization at either site was associated with carriage of
and
In summary, gut colonization by S. aureus was more common than nasal carriage by S. aureus in the studied infants. Gut strains may provide a reservoir for invasive disease in vulnerable individuals. Fibronectin-binding adhesins and other virulence factors may facilitate commensal colonization and confer pathogenic potential.
S. aureus may cause severe infections and frequently colonizes the nose. Nasal carriage of S. aureus increases 3-fold the risk of invasive S. aureus infection. S. aureus is also commonly found in the gut microbiota of infants and young children. However, the relationships between the adhesins and other virulence factors of S. aureus strains and its abilities to colonize the nostrils and gut of infants are not well understood. Our study explores the simultaneous colonization by S. aureus of the nasal and intestinal tracts of newborn infants through 3 years of follow-up. We identify bacterial virulence traits that appear to facilitate persistent colonization of the nose and gut by S. aureus. This expands our current knowledge of the interplay between bacterial commensalism and pathogenicity. Moreover, it may contribute to the development of targeted strategies for combating S. aureus infection.
P fimbria, a mannose-resistant adhesin of uropathogenic Escherichia coli (UPEC), has been shown to be associated with acute pyelonephritis. The pap gene cluster encodes the proteins required for ...P-fimbrial biogenesis, including papG, which encodes the tip adhesin. The three most studied PapG molecular variants, which are shown to bind distinct isoreceptors, are PapGI, -II, and -III. PapGII preferentially binds globoside, or GbO4, a glycolipid isoreceptor of the human kidney. Studies using different animal models of ascending urinary tract infection (UTI) have demonstrated a variable role for P fimbriae, and specifically PapGII-mediated adherence, in renal colonization. The disparities in the results obtained from those studies are likely to be attributed to the differences in animal models and UPEC strains utilized. One explanation that is discussed in detail is the contribution of multiple fimbriae of UPEC that potentially mediate adherence to the mammalian kidney. Overall, P fimbriae appear to play some role in mediating adherence to uroepithelial cells in vivo and establishing an inflammatory response during renal colonization, thus contributing to kidney damage during acute pyelonephritis. To verify that P fimbriae contribute to the pathogenesis of UPEC during ascending UTI (and in particular acute pyelonephritis), future studies should be conducted to satisfy fully all three tenets of the molecular Koch's postulates, including complementation of a mutated allele.
The role of class II P fimbriae (P fimbriae II) in diabetic kidney infections is uncertain, although some genetic and epidemiological studies suggest a lower prevalence of P fimbriae II genes in ...Escherichia coli strains isolated from diabetic patients with complicated kidney infections.
We inoculated a P fimbriae II deficient E. coli (DH5αT) or an isogenic P fimbriae II expressing transformant (DH5αTP) into the bladders of diabetic and non-diabetic BALB/C mice, and sacrificed them after 3 days. The incidence of bladder or kidney infection (≥103 CFU of E. coli per bladder or kidney), bacteremia (≥102 CFU of E. coli on blood culture plate), kidney pathological score, immunoreactive Histo-score (H-score), and corrected H-score (H-score adjusted for Log10 CFU of bacteria in the kidney) were compared among groups.
Diabetic mice were more susceptible to bladder infection than non-diabetic mice with both transformants. The geometric mean of bacteria counts in kidneys was significantly increased only when the diabetic mice were infected with DH5αTP. Among the 4 groups of mice, diabetic mice infected with DH5αTP had the highest incidence of kidney infection and bacteremia, and the highest renal pathology scores. The IL-8 H-score and the corrected IL-6 and IL-8 H-score were significantly lower in diabetic than non-diabetic mice.
We concluded that P fimbriae II contribute to the pathogenesis and severity of E. coli kidney infections in diabetic mice. An impaired cytokine response may also contribute to the increased incidence and severity of kidney infections in diabetic hosts.
is the most common cause of urinary tract infections (UTIs) in children, and yet the underlying mechanisms of virulence and antibiotic resistance and the overall population structure of the species ...is poorly understood within this age group. To investigate whether uropathogenic
(UPEC) from children who developed pyelonephritis carried specific genetic markers, we generated whole-genome sequence data for 96 isolates from children with UTIs. This included 57 isolates from children with either radiologically confirmed pyelonephritis or cystitis and 27 isolates belonging to the well-known multidrug-resistant sequence type ST131, selected to investigate their population structure and antibiotic resistance characteristics. We observed a UPEC population structure that is similar to those reported in adults. In comparison with prior investigations, we found that the full
operon was more common among UPEC from pediatric cases of pyelonephritis. Further, in contrast with recent reports that the P-fimbriae adhesin-encoding
allele is substantially more prevalent in invasive UPEC from adults, we found
was common to both invasive and non-invasive UPEC from children. Among the set of ST131 isolates from children with UTIs, we found antibiotic resistance was correlated with known genetic markers of resistance, as in adults. Unexpectedly, we observed that
30, an allele of the fimbrial gene
often used as a proxy to type ST131 isolates into the most drug-resistant subclade C, was carried by some of the subclade A and subclade B isolates, suggesting that the
30 allele could confer a selective advantage for UPEC. IMPORTANCE Urinary tract infections (UTIs), which are most often caused by
, are not well studied in children. Here, we examine genetic characteristics that differentiate UTI-causing bacteria in children that either remain localized to the bladder or are involved in more serious kidney infections. We also examine patterns of antibiotic resistance among strains from children that are part of
sequence type 131, a group of bacteria that commonly cause UTIs and are known to have high levels of drug resistance. This work provides new insight into the virulence and antibiotic resistance characteristics of the bacteria that cause UTIs in children.
The pks genomic island found in Escherichia coli strains of phylogenetic group B2 encodes colibactin, a polyketide-peptide genotoxin that causes DNA double-strand breaks. We investigated the ...relationship between carriage of the pks island and the capacity of E. coli strains to persist in the gut microbiota of 130 Swedish infants, who were followed from birth to 18 months of age. Long-term colonizers were significantly more likely to have the pks island than either intermediate-term colonizers or transient strains, which suggests that the pks island contributes to the pronounced gut-colonizing capacity of group B2 strains. Long-term persistence in the colon of pks island-containing E. coli strains may be associated with the induction of genomic mutations in the host intestine.
Urinary tract infections are the most common infection in renal transplant patients and Escherichia coli (E. coli) is the most common clinical isolate. Although acute allograft injury (AAI) secondary ...to urinary tract infection (UTI) has been reported, the incidence of AAI associated with UTI, the virulence factors express by uropathic E. coli and whether virulence factors are associated with renal allograft outcome have not been described. We collected E. coli from our renal transplant patients with UTI, determined O:H serotypes, P and Dr fimbriae expression and the clinical presentation and allograft function during the UTI and post‐UTI period. Pyelonephritis occurred in 40% of our patients, 82% of which had AAI (>20% increase in SCr). Sixty‐two percent of E. coli isolates that expressed P fimbriae were associated with AAI, whereas only 29% that did not express P fimbriae had AAI (p = 0.03). The pattern of P fimbriae and O serotypes differed from reported isolates, as the P fimbriae PapG class II and the O25 serotype were the most common. Dr adhesin was expressed on 7 isolates, including 2 of 3 with urosepsis. We propose a unique pattern of uropathogenic serotypes and adherence factors contribute to acute allograft injury in renal transplant patients with UTI.
Among E. coli specimens collected from renal transplant patients with urinary tract infections, the isolates that expressed virulence factors were associated with greater allograft injury.
Cranberry juice (
Vaccinium macrocarpon) is a widely used and recommended North-American folk remedy for prophylaxis of urinary tract infections (UTI). Clinical trials have documented its efficacy in ...women with recurrent UTI, but so far not in other groups of patients. The composition of effective cranberry products and its dosage in UTI prophylaxis have not been defined. Intriguing experimental research has identified an anti-adhesive mechanism of cranberry juice that prevents docking of bacteria on host tissues. This efficacy mechanism can be traced in patients’ urine following oral intake of cranberry products and appears to be due to proanthocyanidins with an A-type linkage of flavanols. The application of this anti-adhesion mechanism of cranberry-proanthocyandins is currently also investigated in other common diseases of bacterial pathogenesis, for example
Helicobacter pylori-associated gastritis and dental caries/periodontal disease. The use of cranberry products appears to be safe and provide additional benefits by anti-oxidant and cholesterol-lowering activity.
Bacterial virulence factors influence the site and severity of urinary tract infections. While pyelonephritis-associated molecular traits have been defined, virulence factors specific for acute ...cystitis strains have not been identified. This study examined the virulence factor repertoire of 247 Escherichia coli strains, prospectively isolated from women with community-acquired acute cystitis. Fim sequences were present in 96% of the isolates, which also expressed Type 1 fimbriae. Curli were detected in 75%, 13% of which formed cellulose. Pap sequences were present in 47%, 27% were papG+, 23% were prsG+ and 42% expressed P fimbriae. TcpC was expressed by 33% of the strains, 32% in a subgroup of patients who only had symptoms of cystitis and 42% in patients with signs of upper urinary tract involvement; most frequently by the papG+/prsG+ subgroup. Strains with the full fim, pap and TcpC and curli virulence profile were more common in cystitis patients with than in patients without upper tract involvement (p<0.05). The varied virulence profile of E. coli strains causing acute cystitis suggests that diverse bacterial strains, expressing Type 1 fimbriae trigger a convergent host response, involving pathways that give rise to the characteristic symptoms of acute cystitis.