ß-lactamase expression induces collateral sensitivity in Escherichia coli.

Major antibiotic groups are losing effectiveness due to the uncontrollable spread of antimicrobial resistance (AMR) genes. Among these, ß-lactam resistance genes -encoding ß-lactamases- stand as the most common resistance mechanism in Enterobacterales due to their frequent association with mobile genetic elements. In this context, novel approaches that counter mobile AMR are urgently needed. Collateral sensitivity (CS) occurs when the acquisition of resistance to one antibiotic increases susceptibility to another antibiotic and can be exploited to eliminate AMR selectively. However, most CS networks described so far emerge as a consequence of chromosomal mutations and cannot be leveraged to tackle mobile AMR. Here, we dissect the CS response elicited by the acquisition of a prevalent antibiotic resistance plasmid to reveal that the expression of the ß-lactamase gene blaOXA-48 induces CS to colistin and azithromycin. We next show that other clinically relevant mobile ß-lactamases produce similar CS responses in multiple, phylogenetically unrelated E. coli strains. Finally, by combining experiments with surveillance data comprising thousands of antibiotic susceptibility tests, we show that ß-lactamase-induced CS is pervasive within Enterobacterales. These results highlight that the physiological side-effects of ß-lactamases can be leveraged therapeutically, paving the way for the rational design of specific therapies to block mobile AMR or at least counteract their effects.

Translational demand is not a major source of plasmid-associated fitness costs.

Plasmids are key drivers of bacterial evolution because they are crucial agents for the horizontal transfer of adaptive traits, such as antibiotic resistance. Most plasmids entail a metabolic burden that reduces the fitness of their host if there is no selection for plasmid-encoded genes. It has been hypothesized that the translational demand imposed by plasmid-encoded genes is a major mechanism driving the fitness cost of plasmids. Plasmid-encoded genes typically present a different codon usage from host chromosomal genes. As a consequence, the translation of plasmid-encoded genes might sequestrate ribosomes on plasmid transcripts, overwhelming the translation machinery of the cell. However, the pervasiveness and origins of the translation-derived costs of plasmids are yet to be assessed. Here, we systematically altered translation efficiency in the host cell to disentangle the fitness effects produced by six natural antibiotic resistance plasmids. We show that limiting translation efficiency either by reducing the number of available ribosomes or their processivity does not increase plasmid costs. Overall, our results suggest that ribosomal paucity is not a major contributor to plasmid fitness costs. This article is part of the theme issue 'The secret lives of microbial mobile genetic elements'.

Epidemiología y etiología de la candidiasis vaginal en mujeres españolas e inmigrantes en Fuenlabrada (Madrid) / Epidemiology and etiology of vulvovaginal candidiasis in Spanish and immigrants' women in Fuenlabrada (Madrid)

OBJETIVOS: La candidiasis vulvovaginal es una infección oportunista provocada por levaduras del género Candida. Los principales factores predisponentes son la gestación, los tratamientos con antibióticos y la diabetes mellitus. Candida albicans es la especie más frecuente, pero en países de África y Asia la frecuencia de Candida no C. albicans es más elevada. Hemos estudiado la distribución de las diferentes especies de Candida en mujeres españolas e inmigrantes. MATERIAL Y MÉTODOS: Estudio retrospectivo de los exudados vaginales recibidos en nuestro laboratorio durante los años 2015 a 2018. RESULTADOS: Se recibieron 2.283 estudios. Se detectó Candida spp. en el 25,7% en españolas y el 28,5% en extranjeras (la diferencia no es significativa). La tasa en inmigrantes es mayor que otras descritas en España. El 82,4% de los aislamientos correspondió a C. albicans. CONCLUSIONES: No hay diferencias significativas entre las tasas de los aislamientos de españolas versus extranjeras. Se observa una demanda proporcionalmente mayor de estudios en las mujeres inmigrantes

OBJECTIVES: Vulvovaginal candidiasis (VVC) is a common vaginal infection. Risk factors include diabetes, antibiotic use and pregnancy. Candida albicans is the most common species identified but non-C. albicans species appear to be more commonly associated with VVC in some Asian and African countries. We had studied the distribution of Candida species in Spanish and immigrants' women residents in Spain. MATERIAL AND METHODS: Retrospective study of vaginal yeast cultures between 2015 and 2018. RESULTS: A total of 2,283 vaginal yeast cultures were collected. Candida spp. was detected in 25.7% from Spanish women and in 28.5% from immigrants (no significant differences). Immigrants have higher rates of vaginal candidiasis compared other studies in Spain. C. albicans was the most common species isolated (82.4%). CONCLUSIONS: There were no differences in vaginal candidiasis rate between Spanish and immigrants' women. Immigrants consulted proportionally more compared with the Spanish women