Publications

The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lung injury and idiopathic pulmonary fibrosis. Although relatively little is known about the function and regulation of claudin tight junction proteins in the lung, new evidence suggests that environmental stimuli can influence claudin expression and alveolar barrier function in human disease. This review considers recent advances in the understanding of the role of claudins in the breakdown of the alveolar epithelial barrier in disease and in epithelial repair.

The accessory Sec systems of streptococci and staphylococci mediate the transport of a family of large, serine-rich glycoproteins to the bacterial cell surface. These systems are comprised of SecA2, SecY2, and three core accessory Sec proteins (Asp1-3). In Streptococcus gordonii, transport of the serine-rich glycoprotein GspB requires both a unique 90-residue N-terminal signal peptide and an adjacent 24-residue segment (the AST domain). We used in vivo site-specific photo-cross-linking to identify proteins that interact with the AST domain during transport. To facilitate this analysis, the entire accessory Sec system of S. gordonii was expressed in Escherichia coli. The determinants of GspB trafficking to the accessory Sec system in E. coli matched those in S. gordonii, establishing the validity of this approach. When the photo-cross-linker was placed within the AST domain, the preprotein was found to cross-link to SecA2. Importantly, no cross-linking to SecA was detected. Cross-linking of the N-terminal end of the AST domain to SecA2 occurred regardless of whether Asp1-3 were present. However, cross-linking to the C-terminal end was dependent on the Asps. The combined results indicate that full engagement of the AST domain by SecA2 is modulated by one or more of the Asps, and suggest that this process is important for initiating transport.

INTRODUCTION

Over the last several years, Neisseria gonorrhoeae has developed decreased susceptibility to extended-spectrum cephalosporins worldwide. Gonococcal antimicrobial surveillance programs in multiple regions have documented the rise in N. gonorrhoeae isolates' minimum inhibitory concentrations to cephalosporins, and the first cases of ceftriaxone treatment failure have been reported. These developments have prompted the use of the term 'superbug' and concerns about the emergence of untreatable gonococcal infections.

AREAS COVERED

Since the publication of the last detailed review of the use of cephalosporins for gonorrhea in 2009, several new developments have occurred, which are detailed in this review. A variety of treatment strategies have been proposed in response to this 'superbug' threat, including increasing the dose or providing multiple doses of cephalosporins, multidrug therapy, rotating therapeutic regimens and individualized treatment based on susceptibility testing.

EXPERT OPINION

A robust public health response is needed that includes better diagnosis and treatment of pharyngeal gonorrhea, improved surveillance of antimicrobial resistance, informed treatment approaches and reduction of the global burden of gonococcal infections.