Abstract
PurposeSalmonella enterica serovar Typhi, the etiological agent of typhoid fever, causes a systemic life-threatening disease. To carry out a successful infection process, this bacterium needs to survive alkaline and acid pH conditions presented in the mouth, stomach, small intestine, and gallbladder. Therefore, in this work, a genetic screening to identify S. Typhi genes involved in acid and circumneutral pH resistance was performed.MethodsA collection of S. Typhi mutants deleted of fragments ranging from 6 to 80 kb were obtained by the Datsenko and Wanner method. Bacterial growth rate assays of each mutant were performed to identify S. Typhi genes involved in circumneutral and acid pH resistance. S. Typhi mutants deficient to growth at specific pH were evaluated in their capacity to invade and replicate in phagocytic cells.ResultsIn this work, it is reported that S. Typhi ∆F4 (pH 4.5), S. Typhi ∆F44 (pH 4.5, 5.5, and 6.5), and S. Typhi ∆F73 (pH 4.5, 5.5, 6.5, and 7.5) were deficient to grow in the pH indicated. These three mutant strains were also affected in their ability to invade and replicate in human macrophages.ConclusionsS. Typhi contains defined genomic regions that influence the survival at specific pH values, as well as the invasion and replication inside human cells. Thus, this genetic information probably allows the bacteria to survive in different human compartments for an efficient infection cycle.
Highlights
Escherichia coli and Salmonella use specific genetic strategies to sense, respond, and survive at diverse pH values present in its human host.E. coli contains five acid-resistance (AR) systems: AR1, which is positively regulated by RpoS and CRP (Bak et al 2014), whereas AR2, AR3, AR4, and AR5 (De BiaseMendoza-Mejía et al Annals of Microbiology (2021) 71:18 the continuous functioning of the decarboxylases
Typhi contains defined genomic regions that influence the survival at specific pH values, as well as the invasion and replication inside human cells
An acid resistance system in E. coli, the glutamine-dependent AR system (Lu et al 2013), is widespread in many bacterial species, including those that are part of the human gut microbiome (Pennacchietti et al 2018). Another mechanism developed by Enterobacteriaceae, including E. coli, for protection against low pH values is known as the acid-tolerance response (ATR) (Blattner et al 1997), defined as the capacity to undergo an adaptive response to moderately acidic pH (4.5–5.8) that enhances the subsequent survival to extreme low pH (3.0) (Álvarez-Ordóñez et al 2011; Audia et al 2001; Foster and Hall 1990)
Summary
Escherichia coli and Salmonella use specific genetic strategies to sense, respond, and survive at diverse pH values present in its human host.E. coli contains five acid-resistance (AR) systems: AR1 (oxidative or glucose-repressed acid resistance system), which is positively regulated by RpoS and CRP (Bak et al 2014), whereas AR2, AR3, AR4, and AR5 (De BiaseMendoza-Mejía et al Annals of Microbiology (2021) 71:18 the continuous functioning of the decarboxylases. An acid resistance system in E. coli, the glutamine-dependent AR system (Lu et al 2013), is widespread in many bacterial species, including those that are part of the human gut microbiome (Pennacchietti et al 2018) Another mechanism developed by Enterobacteriaceae, including E. coli, for protection against low pH values is known as the acid-tolerance response (ATR) (Blattner et al 1997), defined as the capacity to undergo an adaptive response to moderately acidic pH (4.5–5.8) that enhances the subsequent survival to extreme low pH (3.0) (Álvarez-Ordóñez et al 2011; Audia et al 2001; Foster and Hall 1990). A recent report showed that the two-component system CpxRA directly senses acidification through protonation of the CpxA periplasmic histidine residues It activates transcription of the fabA and fabB genes that are essential in biosynthesis of unsaturated fatty acids to enhance the UFA content in membrane lipid, allowing E. coli to grow at acid pH (Xu et al 2020). It has been reported in E. coli that the glycolytic enzymes Glk, PykF, and Pgk are necessary for the rise in ATP under weakly acidic conditions and for survival in markedly acidic conditions (Zhang et al 2020)
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