Blood or Serum Exposure Induce Global Transcriptional Changes, Altered Antigenic Profile, and Increased Cytotoxicity by Classical Bordetellae

Abstract

The classical bordetellae sense and respond to a variety of environments outside and within their mammalian hosts. By causing inflammation and tissue damage, we reasoned that bordetellae are likely to encounter components of blood and/or serum during the course of a respiratory infection, and that detecting and responding to these would be advantageous. Therefore, we hypothesized that classical bordetellae have the ability to sense and respond to blood or serum. Blood or serum exposure resulted in substantial transcriptional changes in Bordetella bronchiseptica, including enhanced expression of many virulence-associated genes. Exposure to blood or serum additionally elicited production of multiple antigens not otherwise detectable, and led to increased bacterial cytotoxicity against macrophages. Transcriptional responses to blood/serum were observed in a Bvg− phase-locked mutant, indicating that the response is not solely dependent on a functional BvgAS system. Similar transcriptional responses to blood/serum were observed for the other classical bordetellae, Bordetella pertussis and Bordetella parapertussis. These data suggest the classical bordetellae respond to signals present in blood and serum by changing their behavior in ways that likely contribute to their remarkable success, via effects on pathogenesis, persistence and/or transmission between hosts.

During bacteremia, Pseudomonas aeruginosa PAO1 adapts by altering the expression of numerous virulence genes including those involved in quorum sensing

“…Previous studies described the influence of whole blood on gene expression in different pathogenic bacteria [111][112][113][114][115][116], who examined Bacillus anthracis, Bordetella pertussis, Streptococcus pyogenes, Staphylococcus aureus, Streptococcus agalactiae, and Enterococcus faecalis, respectively. The type of blood used ranged from bovine [111] to horse [112] to sheep [116] to human [113][114][115].…”

“…Previous studies described the influence of whole blood on gene expression in different pathogenic bacteria [111][112][113][114][115][116], who examined Bacillus anthracis, Bordetella pertussis, Streptococcus pyogenes, Staphylococcus aureus, Streptococcus agalactiae, and Enterococcus faecalis, respectively. The type of blood used ranged from bovine [111] to horse [112] to sheep [116] to human [113][114][115]. Additionally, the expression of the genes of the target organism were examined at radically different times, most ranging from time of inoculation (time 0) to 120 min [112][113][114][115][116] to as long as 4 h [111].…”

“…The type of blood used ranged from bovine [111] to horse [112] to sheep [116] to human [113][114][115]. Additionally, the expression of the genes of the target organism were examined at radically different times, most ranging from time of inoculation (time 0) to 120 min [112][113][114][115][116] to as long as 4 h [111]. The closest of those studies to ours is that of Carlson et al [111] who analyzed the expression of B. anthracis genes by a low inoculum of the bacteria in whole blood for 4 h at 37˚C.…”

Integrated Signaling Pathways Mediate Bordetella Immunomodulation, Persistence, and Transmission

“…The classical Bordetella species, Bordetella bronchiseptica, B. pertussis, and B. parapertussis, can all sense blood and serum components and respond with altered expression of various antigens and increased expression of various known virulence factors and iron scavenging systems. They also change phenotypically, increasing their cytotoxicity likely due to the increased expression of virulence factors such as ACT and/or the type 3 secretion system (T3SS) [35]. Gonyar et al studied those host factors that increase the expression of a particular toxin and found that exposure of B. pertussis to Fetal Bovine Serum, albumin, and calcium increases ACT levels, suggesting that B. pertussis can sense the presence of those two specific serum components and respond by increasing production of ACT which not only works as a hemolysin but also plays a major role in the down-regulation of the host inflammatory response [16].…”

Bordetella Type III Secretion Injectosome and Effector Proteins

“…The bsc -encoded genes of the Bordetella injectosome are induced during infection, and are responsive to blood or serum exposure, and increased CO 2 concentrations (Gaillard et al, 2011 ; Hester et al, 2012 ; Bibova et al, 2015 ; Gestal et al, 2018 ; Van Beek et al, 2018 ; Wong et al, 2019 ). Other stimuli that can activate T3SS expression and secretion in bordetellae are the stringent response induced by iron limitation and/or starvation for carbon source, as depicted in Figure 4 (Brickman et al, 2011 ; Kurushima et al, 2012b ; Hanawa et al, 2016 ).…”