scholarly journals Promising Approach to Inhibit E. coli FimH Adhesion by C-Linked Mannosides

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 1
Author(s):  
Leila Mousavifar ◽  
René Roy

Antagonists of the uropathogenic Escherichia coli type-1 fimbrial adhesin (FimH) are recognized as attractive alternatives for antibiotic therapies and prophylactic strategies against acute and recurrent bacterial infections. [...]

2008 ◽  
Vol 105 (31) ◽  
pp. 10937-10942 ◽  
Author(s):  
L. S. Ronald ◽  
O. Yakovenko ◽  
N. Yazvenko ◽  
S. Chattopadhyay ◽  
P. Aprikian ◽  
...  

2001 ◽  
Vol 126 (1) ◽  
pp. 19-23 ◽  
Author(s):  
F. NOWROUZIAN ◽  
A. E. WOLD ◽  
I. ADLERBERTH

The carriage rate of a range of virulence genes was compared between resident and transient Escherichia coli strains obtained from the rectal flora of 22 home-delivered Pakistani infants 0–6 months old. Genes for the following virulence factors were assessed using multiplex PCR: P, type 1 and S fimbriae, three P fimbrial adhesin varieties, Dr haemagglutinin, K1 and K5 capsule, haemolysin and aerobactin. The E. coli strains examined here differed from those previously obtained from hosts in Western Europe in a lower prevalence of genes for P, S and type 1 fimbriae, K1 capsule and haemolysin. Nevertheless, genes for P fimbriae, the class II variety of papG adhesin, and aerobactin were significantly more common among resident than transient strains, as previously observed in a Swedish study. The results suggest that P fimbriae and aerobactin, previously implicated as virulence factors for urinary tract infection, might contribute to persistence of E. coli in the normal intestinal microflora.


2004 ◽  
Vol 286 (4) ◽  
pp. F795-F802 ◽  
Author(s):  
Lan Mo ◽  
Xin-Hua Zhu ◽  
Hong-Ying Huang ◽  
Ellen Shapiro ◽  
David L. Hasty ◽  
...  

The adhesion of uropathogenic Escherichia coli to the urothelial surface of the bladder is a prerequisite for the establishment of bladder infections. This adhesion process relies on E. coli adhesins and their cognate urothelial receptors, and it also is influenced by an intricate array of defense mechanisms of the urinary system. In this study, we examined the in vivo role of Tamm-Horsfall protein (THP), the most abundant urinary protein, in innate urinary defense. We genetically ablated the mouse THP gene and found that THP deficiency predisposes mice to bladder infections by type 1-fimbriated E. coli. Inoculation of too few type 1-fimbriated E. coli to colonize wild-type mice caused significant bladder colonization in THP-knockout mice. In contrast, THP deficiency did not enhance the ability of P-fimbriated E. coli to colonize the bladder. Our results provide the first in vivo evidence indicating that under physiological conditions, the mannosylated THP can serve as an effective soluble “receptor,” binding to the type 1-fimbriated E. coli and competitively inhibiting them from adhering to the uroplakin Ia receptors present on the urothelial surface. These results suggest that potential THP defects, either quantitative or qualitative, could predispose the urinary bladder to bacterial infections. The generation of THP-deficient mice established the role of THP as a first line of urinary defense and should help elucidate other potential functions of this major protein in urinary tract physiology and diseases.


2015 ◽  
Vol 59 (8) ◽  
pp. 4662-4668 ◽  
Author(s):  
Javier Sánchez-Céspedes ◽  
Emma Sáez-López ◽  
N. Frimodt-Møller ◽  
Jordi Vila ◽  
Sara M. Soto

ABSTRACTFluoroquinolones are among the drugs most extensively used for the treatment of bacterial infections in human and veterinary medicine. Resistance to quinolones can be chromosome or plasmid mediated. The chromosomal mechanism of resistance is associated with mutations in the DNA gyrase- and topoisomerase IV-encoding genes and mutations in regulatory genes affecting different efflux systems, among others. We studied the role of the acquisition of a mutation in thegyrAgene in the virulence and protein expression of uropathogenicEscherichia coli(UPEC). The HC14366M strain carrying a mutation in thegyrAgene (S83L) was found to lose the capacity to cause cystitis and pyelonephritis mainly due to a decrease in the expression of thefimA,papA,papB, andompAgenes. The levels of expression of thefimA,papB, andompAgenes were recovered on complementing the strain with a plasmid containing thegyrAwild-type gene. However, only a slight recovery was observed in the colonization of the bladder in the GyrA complement strain compared to the mutant strain in a murine model of ascending urinary tract infection. In conclusion, a mutation in thegyrAgene of uropathogenicE. colireduced the virulence of the bacteria, likely in association with the effect of DNA supercoiling on the expression of several virulence factors and proteins, thereby decreasing their capacity to cause cystitis and pyelonephritis.


2019 ◽  
Vol 9 (o3) ◽  
Author(s):  
Omar Abdulkareem Ali ◽  
Ruqayah Qubtan Taha

Adhesion is an influential step for bacterial vigor in clinical micro-environments, type 1 fimbriae are essential virulence factors help uropathogenic E. coli in invasion and colonization of uroepithelial cells, the first step of UTIs and biofilm formation. Type 1 fimbriae of E. coli contain FimH protein at the tip encoding via fimH gene cluster, this study was conducted for determination the fimH gene distribution in uro-pathogenic E. coli isolated from UTIs patients. The results of adhesion assay show that (83.6%) of uropathogenic E. coli were high adherent isolates. While the results of E. coli fimH gene amplification prove that, of all E. coli isolates, the fimH gene was found in (87.1%), while among high adherent isolates it was found in (92.6%), and that Shows the function of type 1 fimbriae in the colonization and infection of urinary tracts in addition to other adhesions virulence agents of uropathogenic E. coli.


2012 ◽  
Vol 78 (5) ◽  
pp. 1353-1360 ◽  
Author(s):  
Scott J. Weissman ◽  
James R. Johnson ◽  
Veronika Tchesnokova ◽  
Mariya Billig ◽  
Daniel Dykhuizen ◽  
...  

ABSTRACTMultilocus sequence typing (MLST) is usually based on the sequencing of 5 to 8 housekeeping loci in the bacterial chromosome and has provided detailed descriptions of the population structure of bacterial species important to human health. However, even strains with identical MLST profiles (known as sequence types or STs) may possess distinct genotypes, which enable different eco- or pathotypic lifestyles. Here we describe a two-locus, sequence-based typing scheme forEscherichia colithat utilizes a 489-nucleotide (nt) internal fragment offimH(encoding the type 1 fimbrial adhesin) and the 469-nt internalfumCfragment used in standard MLST. Based on sequence typing of 191 model commensal and pathogenic isolates plus 853 freshly isolated clinicalE. colistrains, this 2-locus approach—which we call CH (fumC/fimH) typing—consistently yielded more haplotypes than standard 7-locus MLST, splitting large STs into multiple clonal subgroups and often distinguishing different within-ST eco- and pathotypes. Furthermore, specific CH profiles corresponded to specific STs, or ST complexes, with 95% accuracy, allowing excellent prediction of MLST-based profiles. Thus, 2-locus CH typing provides a genotyping tool for molecular epidemiology analysis that is more economical than standard 7-locus MLST but has superior clonal discrimination power and, at the same time, corresponds closely to MLST-based clonal groupings.


2001 ◽  
Vol 126 (1) ◽  
pp. 11-18 ◽  
Author(s):  
F. NOWROUZIAN ◽  
I. ADLERBERTH ◽  
A. E. WOLD

Resident and transient Escherichia coli strains from the colonic microflora of 13 Swedish schoolgirls were analysed for carriage of genes encoding a range of adhesins (P, type 1 and S fimbriae, Dr haemagglutinin and three varieties of the P fimbrial papG adhesin) and other virulence traits (K1 and K5 capsule, haemolysin and aerobactin) using multiplex PCR. Forty-four percent of the resident clones carried genes for P fimbriae, K1 or K5 capsule, and aerobactin, compared with only 3% of transient clones (P<0·0001). The P-fimbriated clones most often had the class II variety of the P-fimbrial adhesin gene papG and this adhesin was significantly associated with persistence of a strain. S fimbriae and type 1 fimbriae were equally common in resident and transient strains. The results indicate that not only P fimbriae, but also, certain capsules and the ability to produce the siderophore aerobactin might contribute to persistence of E. coli in the large intestine.


Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 597
Author(s):  
Luca Pierantoni ◽  
Laura Andreozzi ◽  
Simone Ambretti ◽  
Arianna Dondi ◽  
Carlotta Biagi ◽  
...  

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)


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