As recently indiscriminate abuse of existing antibiotics in both clinical and veterinary treatment leads to proliferation of antibiotic resistance in microbes and poses a dilemma for the future treatment of such bacterial infection, antimicrobial resistance has been considered to be one of the currently leading concerns in global public health, and reported to widely spread and extended to a large variety of microorganisms. In China, as one of the currently worst areas for antibiotics abuse, the annual prescription of antibiotics, including both clinical and veterinary treatment, has approaching 140 gram per person and been roughly estimated to be 10 times higher than that in the United Kingdom, which is considered to be a potential area for the emergence of “Super Bugs”. Based on the integrons surveillance in Guangzhou, China in the past decade, this review thus aimed at summarizing the role of integrons in the perspective of both clinical setting and environment, with the focus on the occurrence and prevalence of class 1, 2 and 3 integrons.

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Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans, results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from a polypeptide (Ece1p) encoded by the ECE1 gene, plays a crucial role in driving immunopathology at the vaginal mucosa. This study aimed to determine if expression and/or processing of Ece1p differs across C. albicans isolates and whether this partly underlies differential pathogenicity observed clinically. Using a targeted sequencing approach, we determined that isolate 529L harbors a similarly expressed, yet distinct Ece1p isoform variant that encodes for a predicted functional candidalysin; this isoform was conserved amongst a collection of clinical isolates. Expression of the ECE1 open reading frame (ORF) from 529L in an SC5314-derived ece1Δ/Δ strain resulted in significantly reduced vaginopathogenicity as compared to an isogenic control expressing a wild-type (WT) ECE1 allele. However, in vitro challenge of vaginal epithelial cells with synthetic candidalysin demonstrated similar toxigenic activity amongst SC5314 and 529L isoforms. Creation of an isogenic panel of chimeric strains harboring swapped Ece1p peptides or HiBiT tags revealed reduced secretion with the ORF from 529L that was associated with reduced virulence. A genetic survey of 78 clinical isolates demonstrated a conserved pattern between Ece1p P2 and P3 sequences, suggesting that substrate specificity around Kex2p-mediated KR cleavage sites involved in protein processing may contribute to differential pathogenicity amongst clinical isolates. Therefore, we present a new mechanism for attenuation of C. albicans virulence at the ECE1 locus.