Bill & Melinda Gates Foundation.

The worldwide dissemination of metallo-β-lactamases (MBLs), mediating resistance to carbapenem antibiotics, is a major public health problem. The extent of dissemination of MBLs such as VIM-2, SPM-1 and NDM among Gram-negative pathogens cannot be explained solely based on the associated mobile genetic elements or the resistance phenotype. Here, we report that MBL host range is determined by the impact of MBL expression on bacterial fitness. The signal peptide sequence of MBLs dictates their adaptability to each host. In uncommon hosts, inefficient processing of MBLs leads to accumulation of toxic intermediates that compromises bacterial growth. This fitness cost explains the exclusion of VIM-2 and SPM-1 from Escherichia coli and Acinetobacter baumannii , and their confinement to Pseudomonas aeruginosa . By contrast, NDMs are expressed without any apparent fitness cost in different bacteria, and are secreted into outer membrane vesicles. We propose that the successful dissemination and adaptation of MBLs to different bacterial hosts depend on protein determinants that enable host adaptability and carbapenem resistance.

Mediterranean mussels Mytilus galloprovincialis were experi~nentally cultured from 5 rafts located in 4 Galician Rias, following the established industrial procedure. Cultures were sampled monthly until mussels exceeded market slze. Observation of histological sections of sampled mussels by light microscopy demonstrated symbionts which could be classified into 3 groups according to their pathogenicity. The first group consisted of symbionts with unnoticeable pathogenic effects including: prokaryotic inclusion bodies (PlB) in digestive gland and gills, an unidentified protistan in digestive primary ducts, a kidney coccidian, intracytoplasmic ciliates in digestive tubules, gill ciliates and a turbellarian in the ~ntestinal lumen. The second group comprised syn~bionts that could damage the host, although unlikely to be lethal, including: the microsporidian Steinhausia mytilovum, the flatworm Urastoma cyprinae, and the copepod Mytilicola intestinahs. The third group included the protistan Marteilia refringens and the trematode Proctoeces rnaculatus, potentially lethal pathogens. In addition, mussels with haemocytic infiltration of tissues and granulocytomas and a few cases of disseminated neoplasia were detected. The qualitative composition of mussel symbiont community was similar at the 5 study sites, except for 3 symbionts which were not detected at some sites Quantitatively, symbiont loads were higher and histological signs of stress more abundant in Moana and Vilagarcia (the most inner sites in the Rias), intermediate in Illa de Arousa and Muros, and lower in Lorbe. Symbionts increased in prevalence as mussels grew. Some of the symbionts were detected in mussel seed at the beginning of the experimental cultures.