Parallel evolution leading to impaired biofilm formation in invasive Salmonella strains

Abstract

Pathogenic Salmonella strains that cause gastroenteritis are able to colonize and replicate within the intestines of multiple host species. In general, these strains have retained an ability to form the rdar morphotype, a resistant biofilm physiology hypothesized to be important for Salmonella transmission. In contrast, Salmonella strains that are host-adapted or even host-restricted like Salmonella enterica serovar Typhi, tend to cause systemic infections and have lost the ability to form the rdar morphotype. Here, we investigated the rdar morphotype and CsgD-regulated biofilm formation in two non-typhoidal Salmonella (NTS) strains that caused invasive disease in Malawian children, S . Typhimurium D23580 and S . Enteritidis D7795, and compared them to a panel of NTS strains associated with gastroenteritis, as well as S . Typhi strains. Sequence comparisons combined with luciferase reporter technology identified key SNPs in the promoter region of csgD that either shut off biofilm formation completely (D7795) or reduced transcription of this key biofilm regulator (D23580). Phylogenetic analysis showed that these SNPs are conserved throughout the African clades of invasive isolates, dating as far back as 80 years ago. S . Typhi isolates were negative for the rdar morphotype due to truncation of eight amino acids from the C-terminus of CsgD. We present new evidence in support of parallel evolution between lineages of nontyphoidal Salmonella associated with invasive disease in Africa and the archetypal host-restricted invasive serovar; S . Typhi. We hypothesize that the African invasive isolates are becoming human-adapted and ‘niche specialized’ with less reliance on environmental survival, as compared to gastroenteritis-causing isolates.

In vivo synthesis of bacterial amyloid curli contributes to joint inflammation during S. Typhimurium infection

“…We wanted to determine if the host environment in each infection model provided the activating conditions for curli production. We monitored expression of csgD , encoding the curli transcriptional activator [ 14 , 46 ], using a luciferase reporter strain grown in curli-inducing or non-inducing conditions prior to oral infection of streptomycin pre-treated or untreated C57BL/6 mice. At 96 h post-infection, the GI tract, spleen, and liver were removed and imaged; light production was detected in the GI tracts of all infected mice, but not in the liver and spleen ( Fig 2 ).…”

“…Salmonella and E . coli strains that are associated with invasive disease have generally lost the ability to produce curli and form curli-associated biofilms ([ 46 , 56 ]; summarized in [ 10 ]), which may allow bacteria to spread systemically within the host [ 57 ]. For strains that cause gastroenteritis, studies have shown that curli and flagella are oppositely regulated by the cyclic diguanylate (c-di-GMP) signaling cascade to transition from motility to sessility [ 11 , 58 ].…”

Evolution of Salmonella enterica serotype Typhimurium driven by anthropogenic selection and niche adaptation

“…Many of these genes have been implicated in intestinal colonisation [31,[64][65][66][67][68][69], suggesting that their inactivation in host adapted variants may be associated with a loss of selection for functions no longer required in a reduced host range or where intestinal colonisation is no longer critical to transmission. The sadA and katE, genes are involved in multicellular behaviour, biofilm formation and catalase activity that protects against oxidative stress during high density growth functions, respectively, and are commonly affected by genome degradation in host adapted pathovars of Salmonella [52,70].…”

Ecological niche adaptation of a bacterial pathogen associated with reduced zoonotic potential

“…The loss of ability to form biofilm is a common feature of some host-adapted variants of Salmonella enterica (48,49) (Figure 6D). S. Typhimurium strain SL1344 formed moderate biofilm that was dependent on expression of the csgD gene as previously described (48). The mean biofilm formation for ten U288 strains was not significantly different from that of three ST34 strains.…”