Abstract
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the agents of melioidosis and glanders, respectively, are Tier 1 biothreats. They infect humans and animals, causing disease ranging from acute and fatal to protracted and chronic. Chronic infections are especially challenging to treat, and the identification of in vitro phenotypic markers which signal progression from acute to persistent infection would be extremely valuable. First, a phenotyping strategy was developed employing colony morphotyping, chemical sensitivity testing, macrophage infection, and lipopolysaccharide fingerprint analyses to distinguish Burkholderia strains. Then mouse spleen isolates collected 3–180 days after infection were characterized phenotypically. Isolates from long-term infections often exhibited increased colony morphology differences and altered patterns of antimicrobial sensitivity and macrophage infection. Some of the Bp and Bm persistent infection isolates clearly displayed enhanced virulence in mice. Future studies will evaluate the potential role and significance of these phenotypic markers in signaling the establishment of a chronic infection.
Highlights
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, are classified as Tier 1 bacterial select agents
The development and evaluation of assays to be used for phenotyping animal isolates were conducted using strains that were designated as “prototypes.” For Bm, the chosen strain was Bm ATCC 23344/China 7 and a derivative isolated from a relatively recent case of human glanders, FMH (Srinivasan et al 2001 and Supplementary Table 1)
A relatively small number of strains were fully characterized in vitro and over an extended period in vivo, the strains described represented a diversity of Bp from different patient sources and geographical locations to include the two foci that have been of predominant research concern: Thailand and Northern Australia
Summary
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the etiologic agents of melioidosis and glanders, respectively, are classified as Tier 1 bacterial select agents. Bm is an obligate animal pathogen which causes a debilitating and often fatal zoonotic disease of equines. It has been eradicated in most countries, but is still found in parts of Africa, the Middle East, Eastern Europe, Asia, and South America. Bp is a saprophytic, free-living organism which causes endemic infections in tropical regions such as Southeast Asia and Northern Australia. Both agents can infect humans and animals by several routes. Infections occur upon exposure to contaminated water, soil, or secretions, and through skin abrasions, inhalation, or ingestion. The course of these diseases may range from acute and rapidly fatal to a very protracted and frequently chronic form, as described below (Dance 2014; Gregory and Waag 2008; Welkos et al 2015; Wiersinga et al 2012)
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