Virulence behavior of uropathogenic Escherichia coli strains in the host model Caenorhabditis elegans.
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ABSTRACT:
SUBMITTER: Schifano E
PROVIDER: S-EPMC6562141 | biostudies-literature | 2019 Jun
REPOSITORIES: biostudies-literature
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Virulence behavior of uropathogenic Escherichia coli strains in the host model Caenorhabditis elegans.
Schifano Emily E Marazzato Massimiliano M Ammendolia Maria Grazia MG Zanni Elena E Ricci Marta M Comanducci Antonella A Goldoni Paola P Conte Maria Pia MP Uccelletti Daniela D Longhi Catia C
MicrobiologyOpen 20181031 6
Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Although a number of bacteria can cause UTIs, most cases are due to infection by uropathogenic Escherichia coli (UPEC). UPEC are a genetically heterogeneous group that exhibit several virulence factors associated with colonization and persistence of bacteria in the urinary tract. Caenorhabditis elegans is a tiny, free-living nematode found worldwide. Because many biological pathways are conserved in C. eleg ...[more]
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Project description:BackgroundEscherichia coli lineage ST131 predominates across various spectra of extra-intestinal infections, including urinary tract infection (UTI). The distinctive resistance profile, diverse armamentarium of virulence factors and rapid global dissemination of ST131 E. coli makes it an intriguing pathogen. However, not much is known about the prevalence and genetic attributes of ST131 lineage in Pakistan.MethodsWe estimated prevalence and genetic attributes of E. coli ST131 isolates causing UTI among 155 randomly selected samples. Samples were analyzed for phylogenetic grouping, O-typing and fumC/fimH typing. Isolates were further tested for the ESBL and virulence factors using PCR.ResultsOverall, 59% of the UPEC isolates belonged to the phylogenetic group B2, followed by D = 28%, B1 = 8% and A = 5%. Among 18 different Sequence-types, ST131 was the dominant lineage (n = 71; 46%) out of which 72% of the isolates were assigned to the phylogenetic group B2, while 61% adhered to the serogroup O25b. FumC/fimH typing confirmed 49% of the ST131 as H30 sub-types. In this study, significant numbers of the identified ST131 isolates were MDR and 42% showed ESBL phenotypes, out of which 37% carried bla-CTX-M-15. Moreover, different virulence factors were detected in following percentages: fimH,155(100%), iutA 86 (55%), feoB 76 (49%), papC 75 (48%), papGII 70 (45%), kpsMTII 40 (26%), papEF 37 (24%), fyuA 37 (24%), usp 22 (14%), papA 20 (13%), sfa/foc20 (13%), hlyA 18 (12%), afa 15 (10%), cdtB 11 (7%), papGI 6 (4%), papGIII 6 (4%), kpsMTIII 4 (3%) and bmaE2 (1%).ConclusionConclusively, this study provides important insight into the genetic and virulence attributes of pandemic MDR ST131 strains involved in UTIs. It also highlights higher prevalence of ST131-O25b-H30 UPEC isolates in patients, which was previously unreported from this part of globe.
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Project description:Aeromonad virulence remains poorly understood, and is difficult to predict from strain characteristics. In addition, infections are often polymicrobial (i.e., are mixed infections), and 5-10% of such infections include two distinct aeromonads, which has an unknown impact on virulence. In this work, we studied the virulence of aeromonads recovered from human mixed infections. We tested them individually and in association with other strains with the aim of improving our understanding of aeromonosis. Twelve strains that were recovered in pairs from six mixed infections were tested in a virulence model of the worm Caenorhabditis elegans. Nine isolates were weak worm killers (median time to death, TD50, ≥7 days) when administered alone. Two pairs showed enhanced virulence, as indicated by a significantly shortened TD50 after co-infection vs. infection with a single strain. Enhanced virulence was also observed for five of the 14 additional experimental pairs, and each of these pairs included one strain from a natural synergistic pair. These experiments indicated that synergistic effects were frequent and were limited to pairs that were composed of strains belonging to different species. The genome content of virulence-associated genes failed to explain virulence synergy, although some virulence-associated genes that were present in some strains were absent from their companion strain (e.g., T3SS). The synergy observed in virulence when two Aeromonas isolates were co-infected stresses the idea that consideration should be given to the fact that infection does not depend only on single strain virulence but is instead the result of a more complex interaction between the microbes involved, the host and the environment. These results are of interest for other diseases in which mixed infections are likely and in particular for water-borne diseases (e.g., legionellosis, vibriosis), in which pathogens may display enhanced virulence in the presence of the right partner. This study contributes to the current shift in infectiology paradigms from a premise that assumes a monomicrobial origin for infection to one more in line with the current pathobiome era.
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2021-11-06 | GSE188170 | GEO
Project description:More than half of women will experience a urinary tract infection (UTI), with uropathogenic Escherichia coli (UPEC) causing ~80% of uncomplicated cases. Iron acquisition systems are essential for uropathogenesis, and UPEC strains encode highly diverse iron acquisition systems, underlining their importance. However, a recent UPEC clinical isolate, HM7, lacks this diversity and instead encodes the synthesis pathway for a sole siderophore, enterobactin. To determine if HM7 possesses unidentified iron acquisition systems, we performed RNA sequencing under iron-limiting conditions and demonstrated that the ferric citrate uptake system (fecABCDE and fecIR) was highly upregulated. Importantly, there are high levels of citrate within urine, some of which is bound to iron, and the fec system is enriched in UPEC isolates compared to fecal strains. Therefore, we hypothesized that HM7 and other similar strains use the fec system to acquire iron in the host. Deletion of both enterobactin biosynthesis and ferric citrate uptake (ΔfecA/ΔentB) abrogates use of ferric citrate as an iron source, and fecA provides an advantage in human urine in the absence of enterobactin. However, in a UTI mouse model, fecA is a fitness factor independent of enterobactin production, likely due to the action of host lipocalin-2 chelating ferrienterobactin. These findings indicate that ferric citrate uptake is used as an iron source when siderophore efficacy is limited, such as in the host during UTI. Defining these novel compensatory mechanisms and understanding the nutritional hierarchy of preferred iron sources within the urinary tract are important in the search for new approaches to combat UTI. IMPORTANCE UPEC, the primary causative agent of uncomplicated UTI, is responsible for five billion dollars in health care costs in the United States each year. Rates of antibiotic resistance are on the rise; therefore, it is vital to understand the mechanisms of UPEC pathogenesis to uncover potential targets for novel therapeutics. Iron acquisition systems used to obtain iron from sequestered host sources are essential for UPEC survival during UTI and have been used as vaccine targets to prevent infection. This study reveals the ferric citrate uptake system is another important iron acquisition system that is highly enriched in UPEC strains. Ferric citrate uptake has not previously been associated with UPEC isolates, underlining the importance of the continued study of these strains to fully understand their mechanisms of pathogenesis.
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Project description:While in transit within and between hosts, uropathogenic Escherichia coli (UPEC) encounters multiple stresses, including substantial levels of nitric oxide and reactive nitrogen intermediates. Here we show that UPEC, the primary cause of urinary tract infections, can be conditioned to grow at higher rates in the presence of acidified sodium nitrite (ASN), a model system used to generate nitrosative stress. When inoculated into the bladder of a mouse, ASN-conditioned UPEC bacteria are far more likely to establish an infection than nonconditioned bacteria. Microarray analysis of ASN-conditioned bacteria suggests that several NsrR-regulated genes and other stress- and polyamine-responsive factors may be partially responsible for this effect. Compared to K-12 reference strains, most UPEC isolates have increased resistance to ASN, and this resistance can be substantially enhanced by addition of the polyamine cadaverine. Nitrosative stress, as generated by ASN, can stimulate cadaverine synthesis by UPEC, and growth of UPEC in cadaverine-supplemented broth in the absence of ASN can also promote UPEC colonization of the bladder. These results suggest that UPEC interactions with polyamines or stresses such as reactive nitrogen intermediates can in effect reprogram the bacteria, enabling them to better colonize the host.
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