https://www.id.theclinics.com/article/S0891-5520(13)00074-3/pdf

Urinary Tract Infection Syndromes Occurrence, Recurrence, Bacteriology, Risk Factors, and Disease Burden

Antivirulence drugs are a new type of therapeutic drug that target virulence factors, potentially revitalising the drug-development pipeline with new targets. As antivirulence drugs disarm the pathogen, rather than kill or halt pathogen growth, it has been hypothesized that they will generate much weaker selection for resistance than traditional antibiotics. However, recent studies have shown that mechanisms of resistance to antivirulence drugs exist, seemingly damaging the 'evolution-proof' claim. In this Opinion article, we highlight a crucial distinction between whether resistance can emerge and whether it will spread to a high frequency under drug selection. We argue that selection for resistance can be reduced, or even reversed, using appropriate combinations of target and treatment environment, opening a path towards the development of evolutionarily robust novel therapeutics.

Targeting virulence: can we make evolution-proof drugs?

The bacterial flagellum is a complex apparatus assembled of more than 20 different proteins. The flagellar basal body traverses the cell wall, whereas the curved hook connects the basal body to the whip-like flagellar filament that protrudes several µm from the bacterial cell. The flagellum has traditionally been regarded only as a motility organelle, but more recently it has become evident that flagella have a number of other biological functions. The major subunit, flagellin or FliC, of the flagellum plays a well-documented role in innate immunity and as a dominant antigen of the adaptive immune response. Importantly, flagella have also been reported to function as adhesins. Whole flagella have been indicated as significant in bacterial adhesion to and invasion into host cells. In various pathogens, e.g., Escherichia coli, Pseudomonas aeruginosa and Clostridium difficile, flagellin and/or the distally located flagellar cap protein have been reported to function as adhesins. Recently, FliC of Shiga-toxigenic E. coli was shown to be involved in cellular invasion via lipid rafts. Here, we examine the latest or most important findings regarding flagellar adhesive and invasive properties, especially focusing on the flagellum as a potential virulence factor.

The Role of the Bacterial Flagellum in Adhesion and Virulence

The details of all steps involved in the quantification of
biofilm formation in microtiter plates are described. The
presented protocol incorporates information on assessment of
biofilm production by staphylococci, gained both by direct
experience as well as by analysis of methods for assaying
biofilm production. The obtained results should simplify
quantification of biofilm formation in microtiter plates, and
make it more reliable and comparable among different
laboratories.

Quantification of biofilm in microtiter plates: overview oftesting conditions and practical recommendations for assessmentof biofilm production by staphylococci.

Multidrug resistance in Escherichia coli has become a worrying issue that is increasingly observed in human but also in veterinary medicine worldwide. E. coli is intrinsically susceptible to almost all clinically relevant antimicrobial agents, but this bacterial species has a great capacity to accumulate resistance genes, mostly through horizontal gene transfer. The most problematic mechanisms in E. coli correspond to the acquisition of genes coding for extended-spectrum β-lactamases (conferring resistance to broad-spectrum cephalosporins), carbapenemases (conferring resistance to carbapenems), 16S rRNA methylases (conferring pan-resistance to aminoglycosides), plasmid-mediated quinolone resistance (PMQR) genes (conferring resistance to [fluoro]quinolones), and mcr genes (conferring resistance to polymyxins). Although the spread of carbapenemase genes has been mainly recognized in the human sector but poorly recognized in animals, colistin resistance in E. coli seems rather to be related to the use of colistin in veterinary medicine on a global scale. For the other resistance traits, their cross-transfer between the human and animal sectors still remains controversial even though genomic investigations indicate that extended-spectrum β-lactamase producers encountered in animals are distinct from those affecting humans. In addition, E. coli of animal origin often also show resistances to other-mostly older-antimicrobial agents, including tetracyclines, phenicols, sulfonamides, trimethoprim, and fosfomycin. Plasmids, especially multiresistance plasmids, but also other mobile genetic elements, such as transposons and gene cassettes in class 1 and class 2 integrons, seem to play a major role in the dissemination of resistance genes. Of note, coselection and persistence of resistances to critically important antimicrobial agents in human medicine also occurs through the massive use of antimicrobial agents in veterinary medicine, such as tetracyclines or sulfonamides, as long as all those determinants are located on the same genetic elements.

/pdf/antimicrobial-resistance-in-escherichia-coli-p14z5a8h4w.pdf

Antimicrobial resistance in Escherichia coli.

What defines extraintestinal pathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the most common cause of community- and hospital-acquired urinary tract infections (UTIs). Isolates from uncomplicated community-acquired UTIs express a variety of virulence traits that promote the efficient colonization of the urinary tract. In contrast, nosocomial UTIs can be caused by E. coli strains that differ in their virulence traits from the community-acquired UTI isolates. UPEC virulence markers are used to distinguish these facultative extraintestinal pathogens, which belong to the intestinal flora of many healthy individuals, from intestinal pathogenic E. coli (IPEC). IPEC is a diarrheagenic pathogen with a characteristic virulence gene set that is absent in UPEC. Here, we characterized 265 isolates from patients with UTIs during inpatient or outpatient treatment at a hospital regarding their phylogenies and IPEC or UPEC virulence traits. Interestingly, 28 of these isolates (10.6%) carried typical IPEC virulence genes that are characteristic of enteroaggregative E. coli (EAEC), Shiga toxin-producing E. coli (STEC), and atypical enteropathogenic E. coli (aEPEC), although IPEC is not considered a uropathogen. Twenty-three isolates harbored the astA gene coding for the EAEC heat-stable enterotoxin 1 (EAST1), and most of them carried virulence genes that are characteristic of UPEC and/or EAEC. Our results indicate that UPEC isolates from hospital patients differ from archetypal community-acquired isolates from uncomplicated UTIs by their spectrum of virulence traits. They represent a diverse group, including EAEC, as well as other IPEC pathotypes, which in addition contain typical UPEC virulence genes. The combination of typical extraintestinal pathogenic E. coli (ExPEC) and IPEC virulence determinants in some isolates demonstrates the marked genome plasticity of E. coli and calls for a reevaluation of the strict pathotype classification of EAEC.

https://journals.asm.org/doi/pdf/10.1128/JCM.02069-13

Characterization of Escherichia coli Isolates from Hospital Inpatients or Outpatients with Urinary Tract Infection

Asymptomatic bacteriuria (ABU) is a condition where bacteria stably colonize the urinary tract, in a manner closely resembling commensalism at other mucosal sites. The patients carry >105 CFU/ml for extended periods of time and rarely develop symptoms. Contrasting the properties of ABU strains to those of uropathogenic isolates causing symptomatic infection is therefore highly relevant to understand mechanisms of bacterial adaptation. The prototype ABU strain Escherichia coli 83972 has a smaller genome than uropathogenic E. coli (UPEC) strains with deletions or point mutations in several virulence genes, suggesting that ABU strains undergo a programmed reductive evolution within human hosts. This study addressed if these observations can be generalized. Strains causing ABU in outpatients or hospitalized patients after catheterization or other invasive procedures were compared to commensal E. coli isolates from the intestinal flora of healthy individuals. Notably, clonal complex 73 (CC73) was a prominent phylogenetic lineage dominated by ABU isolates. ABU isolates from outpatients and hospitalized patients had a similar overall virulence gene repertoire, which distinguished them from many commensals, but typical UPEC virulence genes were less frequently attenuated in hospital strains than in outpatient strains or commensals. The decreased virulence potential of outpatient ABU isolates relative to that of ABU strains from hospitalized patients supports the hypothesis that loss of expression or decay of virulence genes facilitates long-term carriage and adaptation to host environments.

https://iai.asm.org/content/iai/80/2/668.full.pdf

Comparison of Asymptomatic Bacteriuria Escherichia coli Isolates from Healthy Individuals versus Those from Hospital Patients Shows that Long-Term Bladder Colonization Selects for Attenuated Virulence Phenotypes

Christian-Daniel Köhler

Papers

What defines extraintestinal pathogenic Escherichia coli

Characterization of Escherichia coli Isolates from Hospital Inpatients or Outpatients with Urinary Tract Infection

Comparison of Asymptomatic Bacteriuria Escherichia coli Isolates from Healthy Individuals versus Those from Hospital Patients Shows that Long-Term Bladder Colonization Selects for Attenuated Virulence Phenotypes