Disarming One of the Deadliest Pathogens
Francisella tularensis, the cause of tularemia and one of the deadliest respiratory pathogens in existence, is considered a potential biological weapon because it is readily aerosolized and exhibits a high degree of infectivity and lethality in humans. While a live attenuated vaccine strain has been developed, it remains unlicensed because scientists have been unable to understand the basis for its attenuated virulence. In an attempt to find an acceptable live attenuated vaccine strain, researchers from Harvard Medical School examined the mechanism behind one reason the pathogen is so lethal. The first line of defense against a bacterial pathogen is innate immunity, which slows the progress of infection to allow time for adaptive immunity to develop. F. tularensis suppresses the early innate immune response, allowing the pathogen to kill its host before adaptive immunity develops, using a specific lipopolysaccharide (LPS.) In this study the researchers show that a strain of the pathogen lacking this specific LPS is attenuated in mice and specifically elicits an innate immune response. When immunized with the strain, mice were protected against challenge by a highly virulent strain of the bacteria. This study has identified not only a novel LPS modification important for microbial virulence, but also offers a new vaccine candidate.
Lessons from a Decade of Plague in a Port City
A cluster of human plague cases over a 10-year period in the seaport city of Mahajanga Madagascar after a 62-year plague-free period provided researchers from Arizona and Madagascar with an opportunity to study plague dynamics in an urban environment, especially since historically plague entered new geographic areas through port cities such as this. Most of the isolates found during the outbreak were very closely related, suggesting that a single introduction became established in Mahajanga and then underwent local cycling and differential. The ultimate extinction of plague in Mahajanga suggests that although plague pathogens’ ability to invade port cities has been essential for intercontinental spread, these regions are not a suitable long-term niche. However, the temporary large pathogen population expansion provides the means for plague pathogens to disperse and become ecologically established in more suitable nonurban environments.
Gene Library for Staph
To enhance the research capabilities of investigators interested in Staphylococcus aureus, the Nebraska Center for Staphylococcal Research (CSR) has generated a sequence-defined transposon mutant library consisting of 1,952 strains, each containing a single mutation within a nonessential gene of the epidemic community-associated methicillin-resistant S. aureus (CA-MRSA) isolate USA300. Infections caused by S. aureus cause significant morbidity and mortality in both community and hospital environments. Specific-allelic-replacement mutants are required to study the biology of this organism; however, this process is costly and time-consuming. In this paper the researchers describe the construction and validation of a sequence-defined transposon mutant library available for use by the scientific community through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) strain repository. Overall, this library and associated tools will have a significant impact on studies investigating S. aureus pathogenesis and biology and serve as a useful paradigm for the study of other bacterial systems.
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