BackgroundGroup B Streptococcus (GBS) serotype (Ia, Ib, II-IX) correlates with pathogen virulence and clinical prognosis. Epidemiological studies of seroprevalence are an important metric for determining the proportion of serotypes in a given population. The purpose of this study was to evaluate the prevalence of individual GBS serotypes at Madigan Healthcare System (Madigan), the largest military tertiary healthcare facility in the Pacific Northwestern United States, and to compare seroprevalences with international locations.MethodsTo determine serotype distribution at Madigan, we obtained GBS isolates from standard-of-care anogenital swabs from 207 women of indeterminate gravidity between ages 18-40 during a five month interval. Serotype was determined using a recently described molecular method of polymerase chain reaction by capsular polysaccharide synthesis (cps) genes associated with pathogen virulence.ResultsSerotypes Ia, III, and V were the most prevalent (28%, 27%, and 17%, respectively). A systematic review of global GBS seroprevalence, meta-analysis, and statistical comparison revealed strikingly similar serodistibution at Madigan relative to civilian-sector populations in Canada and the United States. Serotype Ia was the only serotype consistently higher in North American populations relative to other geographic regions (p < 0.005). The number of non-typeable isolates was significantly lower in the study (p < 0.005).ConclusionThis study establishes PCR-based serotyping as a viable strategy for GBS epidemiological surveillance. Our results suggest that GBS seroprevalence remains stable in North America over the past two decades.

Acinetobacter baumannii is responsible for 10% of all nosocomial infections and has >50% mortality rates when causing ventilator-associated pneumonia. In this proof-of-concept study, we evaluated SPR741, an antibiotic adjuvant that permeabilizes the Gram-negative membrane, in combination with rifampin against AB5075, an extensively drug-resistant (XDR) A. baumannii strain. In standard in vitro assays and in a murine pulmonary model, we found that this drug combination can significantly reduce bacterial burden and promote animal survival despite an aggressive infection.

Background Pseudomonas aeruginosa possesses an array of virulence genes ensuring successful infection development. A two-partner secretion system Exolysin BA (ExlBA) is expressed in the PA7-like genetic outliers consisting of ExlA, a pore-forming toxin and ExlB transporter protein. Presence of exlBA in multidrug-resistant (MDR) strains has not been investigated, particularly in the strains isolated from wounded soldiers. Methods We screened whole genome sequences of 2439 MDR- P. aeruginosa strains for the presence of exlBA. We compiled all exlBA positive strains and compared them with a diversity set for demographics, antimicrobial profiles and phenotypic characteristics: surface motility, biofilm formation, pyocyanin production and hemolysis. We compared the virulence of strains with comparable phenotypic characteristics in Galleria mellonella. Results We identified 33 exlBA-positive strains (1.5%). These strains have increased antibiotic resistance, they are more motile, produce more robust biofilms and have comparable pyocianin production with the diversity set despite the phenotypic differences within the group. In in vivo infection models, these strains were less virulent than Type III Secretion System (T3SS) positive counterparts. Conclusions exlBA-positive strains are wide spread among the PA7-like outliers. While not as virulent as strains possessing T3SS, these strains exhibit phenotypic features associated with virulence and are still lethal in vivo.

Objective: To better understand Acinetobacter baumannii pathogenesis and to advance drug discovery against this pathogen, we developed a porcine, full-thickness, excisional, monospecies infection wound model.Approach: The research was facilitated with AB5075, a previously characterized, extensively drug-resistant A. baumannii isolate. The model requires cyclophosphamide-induced neutropenia to establish a skin and soft tissue infection (SSTI) that persists beyond 7 days. Multiple, 12-mm-diameter full-thickness wounds were created in the skin overlying the cervical and thoracic dorsum. Wound beds were inoculated with 5.0 × 104 colony-forming units (CFU) and covered with dressing.Results: A. baumannii was observed in the wound bed and on the dressing in what appeared to be biofilm. When bacterial burdens were measured, proliferation to at least 106 CFU/g (log106) wound tissue was observed. Infection was further characterized by scanning electron microscopy (SEM) and peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) staining. To validate as a treatment model, polymyxin B was applied topically to a subset of infected wounds every 2 days. Then, the treated and untreated wounds were compared using multiple quantitative and qualitative techniques to include gross pathology, CFU burden, histopathology, PNA-FISH, and SEM.Innovation: This is the first study to use A. baumannii in a porcine model as the sole infectious agent.Conclusion: The porcine model allows for an additional preclinical assessment of antibacterial candidates that show promise against A. baumannii in rodent models, further evaluating safety and efficacy, and serve as a large animal in preclinical assessment for the treatment of SSTI.

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