Extraintestinal Pathogenic : Beta-Lactam Antibiotic and Heavy Metal Resistance.

Multiple-antibiotic-resistant (MAR) extra-intestinal pathogenic (ExPEC) represents one of the most frequent causes of human nosocomial and community-acquired infections, whose eradication is of major concern for clinicians. ExPECs may inhabit indefinitely as commensal the gut of humans and other animals; from the intestine, they may move to colonize other tissues, where they are responsible for a number of diseases, including recurrent and uncomplicated UTIs, sepsis and neonatal meningitis. In the pre-antibiotic era, heavy metals were largely used as chemotherapeutics and/or as antimicrobials in human and animal healthcare. As with antibiotics, the global incidence of heavy metal tolerance in commensal, as well as in ExPEC, has increased following the ban in several countries of antibiotics as promoters of animal growth. Furthermore, it is believed that extensive bacterial exposure to heavy metals present in soil and water might have favored the increase in heavy-metal-tolerant microorganisms. The isolation of ExPEC strains with combined resistance to both antibiotics and heavy metals has become quite common and, remarkably, it has been recently shown that heavy metal resistance genes may co-select antibiotic-resistance genes. Despite their clinical relevance, the mechanisms underlining the development and spread of heavy metal tolerance have not been fully elucidated. The aim of this review is to present data regarding the development and spread of resistance to first-line antibiotics, such as beta-lactams, as well as tolerance to heavy metals in ExPEC strains.