José Antonio Escudero García-Calderón defendió su tesis doctoral en la Facultad de Veterinaria de la Universidad Complutense de Madrid

7 de octubre de 2011

Streptococcus suis is a worldwide-distributed zoonotic agent affecting pig and man. In industrialized countries it is mainly regarded as an important economic burden to the pig industry that only sporadically causes infections in humans. Nevertheless, in several developing countries in South East Asia, S. suis is one of the main causes of meningitis in humans. Also, S. suis has been reported as the causative agent of large, high-mortality outbreaks among the Chinese population, during the summers of 1998, 1999 and 2005. Mortality was high as a result of the onset of a Toxic Shock Syndrome. Although classically considered an occupational zoonosis, recent data points to the possibility of foodborne transmission of S. suis. Consequently, concern about this pathogen has risen in these areas, and measures to prevent or hinder its impact are needed.

Antimicrobial resistance is a major threat for modern medicine, as many interventions, from routine to cutting-edge techniques, depend on the efficacy of antibiotics. Fluoroquinolones are one of the most important families of antibiotics in clinical practice, and measures should be taken to preserve their usefulness. The fight against antimicrobial resistance relies on the early detection of resistant strains and the elucidation of the genetic basis of resistance.

In this Thesis two genetic mechanisms of fluoroquinolone (FQ) resistance have been characterized in Streptococcus suis. The main mechanism is the presence of mutations in the quinolone resistance-determining regions (QRDR) of the genes encoding the antibiotic targets, gyrA and parC. Accumulation of mutations is a step-wise phenomenon that leads to high-level resistance. Interestingly an efflux mechanism was also found and elucidated. FQ efflux in S. suis is due to the overexpression of SatAB, a narrow spectrum norfloxacin and ciprofloxacin ABC-efflux pump. The interruption of satR, a local repressor of the pump, leads to enhanced efflux and is sufficient to mediate clinically-relevant resistance to fluoroquinolones.