All authors read and approved the final manuscript.”
“Background Cholera is a severe disease characterized by watery diarrhea that is caused by the gram-negative bacterium V. cholerae. The massive diarrhea experienced by patients is mainly due to the colonization of toxigenic V. cholerae strains in the small intestine and their production of cholera toxin (CT) [1]. Cholera continues to be a major public health concern in many developing countries [2, 3]. Outbreaks of cholera have been increasing globally in the past decade, most recently in Haiti [4]. V. cholerae

is CRT0066101 naturally present in the environment and autochthonous to coastal and estuarine ecosystems. Based on the heat-stable somatic O antigen, the species V. cholerae is divided into more than 200 Z-DEVD-FMK clinical trial serogroups [5, 6]. Only two serogroups, O1 and O139, have thus far been demonstrated to cause epidemic and pandemic cholera. Seven pandemics caused by V. cholerae O1 have been reported since 1871. V. cholerae O139 emerged in late 1992 on the India subcontinent [7, 8]. V. cholerae O1 exists as two biotypes, classical and El Tor, which are distinguished by a variety of phenotypic markers, and differ in Temsirolimus supplier the severity of their infections and ability to

survive outside the human intestine as well [3, 9–11]. Two of the first six cholera pandemics are known to have been caused by the classical biotype, while the ongoing seventh pandemic, which began in 1961, is caused by the El Tor biotype. The vast majority of strains within the O1 serogroup display one of two serotypes, Ogawa or Inaba. A third serotype called Hikojima also exists, but is rare and unstable

and not recognized by some authorities [3]. The Ogawa and Inaba serotypes differ by the presence of a 2-O-methyl group in the nonreducing terminal carbohydrate in the Ogawa O antigen [12, 13]. The O antigen is not a primary gene product, but rather, an assemblage of sugar moieties. The genes responsible for the synthesis of the O1-specific antigens are present in a cluster designated the rfb region [14]. P-type ATPase Genetic changes in this region are correlated with specific somatic antigens which are serologically different. The serogroup O139 resulted from a 22 kb deletion of the rfb region of an O1 El Tor strain, with replacement by a 35 kb wbf region encoding the O139 specific O antigen [15]. Serotype conversion within the O1 serogroup has been demonstrated to occur during subculture in vitro, passage in vivo, epidemics and during phage treatment [16–21]. Genetic alterations in the rfbT gene account for the serotype shift which encodes a transferase responsible for the expression of the Ogawa-specific antigen [19, 22, 23]. Site-specific sequence mutations causing a frameshift in the rfbT gene, thus producing truncated RfbT proteins, were previously detected in Inaba strains [19, 22, 24]. Generally, the serotype shift occurs more frequently in the direction of Ogawa to Inaba [3].