Acid Resistance in Francisella tularensis

Abstract

Francisella tularensis, the etiologic agent of tularemia, can survive under acidic conditions. Tularemia can be acquired by several routes, including by ingestion of contaminated food or water. While acid resistance is usually associated with a low oral infective dose (ID), the ID for gastrointestinal illness is quite high. In this study, four strains of F. tularensis ssp. tularensis (type A) and four strains of F. tularensis ssp. holarctica (type B) were examined for innate acid resistance and the ability to survive in synthetic gastric fluid (SGF) under in vitro conditions similar to passage through the human stomach. Survival for all strains was significantly less in pH 2.5 SGF than in pH 2.5 phosphate-buffered saline and pH 4.0 SGF. Attenuated strains were consistently less resistant. Type B strains are most often associated with waterborne outbreaks and were examined after storage in natural water. Low-nutrient preadaptation resulted in increased resistance. Although F. tularensis can persist under certain acidic conditions, it is sensitive to conditions replicating the fasting human stomach. This may help explain the high ID required for gastrointestinal infections.

A study of innate immune kinetics reveals a role for a chloride transporter in a virulent Francisella tularensis type B strain

“…While ClcA and ClcB in E. coli are believed to have different pH optima (Chris Miller, personal correspondence), there is no redundant gene in Francisella . Several F. tularensis type B strains, including OR96‐0246, were previously examined for gastric acid resistance, but may not appropriately reflect conditions during a macrophage infection (Adcock et al, 2014 ). Furthermore, while reductions in viability were observed for cultures exposed to SGF (synthetic gastric fluid, pH 2.5 and 4.0) compared to acidic PBS (pH 2.5), survival was nonetheless higher for WT strains than for attenuated strains such as LVS.…”

“…Brown et al monitored serum from North American cottontail rabbits infected with type B strains OR96‐0246 and KY99‐3387 and reported a strong humoral response in rabbits that survived the past 14 days (Brown et al, 2015 ). Many studies of virulent type B strains typically focus on clinical or diagnostic aspects of tularemia but lack mechanistic insights (Adcock et al, 2014 ; Fritzsch & Splettstoesser, 2010 ; Johansson et al, 2000 , 2014 ; Stenmark et al, 2003 ; Versage et al, 2003 ).…”

Long-Term Survival of Virulent Tularemia Pathogens outside a Host in Conditions That Mimic Natural Aquatic Environments

“…tularensis and F. tularensis subsp. holarctica show relatively high survival following temporal acid treatment ( 37 , 38 ), and low-nutrient preadaptation in natural water resulted in even greater acid resistance ( 38 ).…”

Occurrence and Control of Tularemia in Drinking Water

“…At the least favorable condition of 5°C and pH 8.0, a mean C × T of 76.1 mg‐min/L was required to achieve a 4 log 10 level of inactivation. F. tularensis was more resistant to inactivation by free chlorine than other vegetative bacterial biothreat agents and other waterborne bacterial pathogens (Rose & Rice 2014).…”

“…The 50% infective dose (the dose required for 50% infectivity) required for gastrointestinal infection in humans has been reported to be 10 8 colony-forming units (cfu) (Hornick et al 1966). The organism exhibits a degree of innate acid resistance (Humrighouse et al 2011), but laboratory studies have found that the bacterium is susceptible to conditions that would normally be encountered in the human stomach (Adcock et al 2014). Gastrointestinal symptoms can sometimes also result from tularemia acquired by means other than ingestion, such as arthropod bites-e.g., ticks (Zaidi & Singer 2002).…”