We would like to thank Prof. Anne O. Summers (The University of Georgia, Athens, USA) for

providing the original E. casseliflavus 664.1H1 isolate and Dr Carla Novais (Fernando Pessoa University, Oporto, Portugal) for critically reading the manuscript. “
“Ramoplanin is a lipoglycodepsipeptide antimicrobial active against clinically important Gram-positive bacteria signaling pathway including methicillin-resistant Staphylococcus aureus. To proactively examine ramoplanin resistance, we subjected S. aureus NCTC 8325-4 to serial passage in the presence of increasing concentrations of ramoplanin, generating the markedly resistant strain RRSA16. Susceptibility testing of RRSA16 revealed the unanticipated acquisition of cross-resistance to vancomycin and nisin. RRSA16 displayed Selleckchem Enzalutamide phenotypes, including a thickened cell wall and reduced susceptibility to Triton X-100-induced autolysis, which are associated with vancomycin intermediate-resistant S. aureus strains. Passage of RRSA16 for 18 days in a drug-free medium yielded strain R16-18d with restored antibiotic susceptibility. The RRSA16 isolate may be used to identify the genetic and biochemical basis for ramoplanin resistance and to further our understanding of the evolution of antibiotic cross-resistance mechanisms

in S. aureus. Staphylococcus aureus is the frequent causative agent of hospital- and community-acquired infections. In 2005, there were an estimated 94 360 invasive methicillin-resistant Nintedanib (BIBF 1120) S. aureus (MRSA) cases and an estimated 18 650 deaths in the United States due to these infections (Klevens et al., 2007). Most alarming is the observation that in 2005, the number of deaths in the United States attributed to

MRSA infections exceeded the total number of US deaths attributable to HIV/AIDS (Bancroft, 2007; Klevens et al., 2007). Ramoplanin is a lipoglycodepsipeptide antibiotic active against clinically important Gram-positive bacteria including vancomycin-resistant Enterococcus sp., MRSA and vancomycin intermediate-resistant Clostridium difficile (Neu & Neu, 1986; Jones & Barry, 1989; Biavasco et al., 1991; Johnson et al., 1992; Mobarakai et al., 1994; Ristow et al., 1995; Rolston et al., 1996; Finegold et al., 2004; Pelaez et al., 2005). Preclinical studies have demonstrated that ramoplanin exerted a rapid bactericidal effect on S. aureus biofilms (Opperman et al., 2003) and that a clinical vancomycin-resistant S. aureus strain containing the vanA gene was susceptible to ramoplanin (Bozdogan et al., 2003). In the immediate past, ramoplanin was evaluated as a possible treatment for infection from these microorganisms, and in Asia, the structurally related antibiotic enduracidin has been in use as a growth-promoting feed additive for livestock (McCafferty et al., 2002). Treatment options for MRSA infections are limited as many MRSA strains are resistant to multiple antimicrobial agents (Ayliffe, 1997).