Exploiting human immune repertoire transgenic mice for protective monoclonal antibodies against antimicrobial resistant Acinetobacter baumannii.

The use of monoclonal antibodies for the control of drug resistant nosocomial bacteria may alleviate a reliance on broad spectrum antimicrobials for treatment of infection. We identify monoclonal antibodies that may prevent infection caused by carbapenem resistant Acinetobacter baumannii. We use human immune repertoire mice (Kymouse platform mice) as a surrogate for human B cell interrogation to establish an unbiased strategy to probe the antibody-accessible target landscape of clinically relevant A.

Intranasal immunization with outer membrane vesicles (OMV) protects against airway colonization and systemic infection with Acinetobacter baumannii.

Objectives: The multidrug-resistant bacteria Acinetobacter baumannii is a major cause of hospital-associated infection; a vaccine could significantly reduce this burden. The aim was to develop a clinically relevant model of A. baumannii respiratory tract infection and to test the impact of different immunization routes on protective immunity provided by an outer membrane vesicle (OMV) vaccine.

The prevalence and implications of single nucleotide polymorphisms in genes encoding the RNA polymerase of clinical isolates of Staphylococcus aureus.

Central to the regulation of bacterial gene expression is the multisubunit enzyme RNA polymerase (RNAP), which is responsible for catalyzing transcription. As all adaptive processes are underpinned by changes in gene expression, the RNAP can be considered the major mediator of any adaptive response in the bacterial cell. In bacterial pathogens, theoretically, single nucleotide polymorphisms (SNPs) in genes that encode subunits of the RNAP and associated factors could mediate adaptation and confer a selective advantage to cope with biotic and abiotic stresses.

Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug.

Expression of β-lactamase is the single most prevalent determinant of antibiotic resistance, rendering bacteria resistant to β-lactam antibiotics. In this article, we describe the development of an antibiotic prodrug that combines ciprofloxacin with a β-lactamase-cleavable motif. The prodrug is only bactericidal after activation by β-lactamase.

Naturally occurring polymorphisms in the virulence regulator Rsp modulate Staphylococcus aureus survival in blood and antibiotic susceptibility.

Nasal colonization by the pathogen Staphylococcus aureus is a risk factor for subsequent infection. Loss of function mutations in the gene encoding the virulence regulator Rsp are associated with the transition of S. aureus from a colonizing isolate to one that causes bacteraemia.

What role does the quorum-sensing accessory gene regulator system play during Staphylococcus aureus bacteremia?

Staphylococcus aureus is a major cause of bacteremia, which frequently results in serious secondary infections such as infective endocarditis, osteomyelitis, and septic arthritis. The ability of S. aureus to cause such a wide range of infections has been ascribed to its huge armoury of different virulence factors, many of which are under the control of the quorum-sensing accessory gene regulator (Agr) system.

Growth inhibition of pathogenic bacteria by sulfonylurea herbicides.

Emerging resistance to current antibiotics raises the need for new microbial drug targets. We show that targeting branched-chain amino acid (BCAA) biosynthesis using sulfonylurea herbicides, which inhibit the BCAA biosynthetic enzyme acetohydroxyacid synthase (AHAS), can exert bacteriostatic effects on several pathogenic bacteria, including Burkholderia pseudomallei, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our results suggest that targeting biosynthetic enzymes like AHAS, which are lacking in humans, could represent a promising antimicrobial drug strategy.