The two-component system CpxA/CpxR is critical for full virulence in Actinobacillus pleuropneumoniae

Abstract

Actinobacillus pleuropneumoniae, a major bacterial porcine respiratory tract pathogen causing pig pleuropneumonia, has resulted in high economic losses worldwide. The mutation of the two-component system CpxAR strongly impacted the virulence of A. pleuropneumoniae, but the underlying regulatory mechanism remained unclear. Here, we found that CpxAR positively regulated the cpxDCBA gene cluster involved in polysaccharide capsule export. A capsular layer was confirmed in wild-type cells by transmission electron microscopy, whereas cpxAR and cpxD mutants were non-capsulated. The mutants for polysaccharide capsule export gene cpxD exhibited non-capsulated and were strongly impaired in virulence for mice, indicating a major role of CPS export system in virulence. We then demonstrated that CpxR directly regulated the transcription of the CPS export gene cluster cpxDCBA. Taken together, our data suggested that CpxAR is a key modulator of capsule export that facilitates A. pleuropneumoniae survival in the host.

Identification of Antibacterial Components and Modes in the Methanol-Phase Extract from a Herbal Plant Potentilla kleiniana Wight et Arn

“…For instance, the DEGs ( cpxAR, WU75_18570, and WU75_18575 ) encoding a two-component sensor protein and a transcriptional regulator were strongly up-regulated (10.981-fold and 26.500-fold) ( p < 0.05). The CpxAR is a key modulator of capsule export that facilitates Actinobacillus pleuropneumoniae survival in the host [ 49 ]. It also regulates cell membrane permeability and efflux pump activity and induces multidrug resistance (MDR) in Salmonella enteritidis [ 50 ].…”

Examination of the Virulence of Actinobacillus pleuropneumoniae Serovar 16 in Pigs

“…The toxicity of these toxins is different: ApxI and ApxIII are strongly cytotoxic, while ApxII is moderately toxic [ 20 ], which can explain the differences in virulence. Quantification of other virulence factors, such as fimbriae, lipopolysaccharides, glycosphingolipids, outer membrane proteins, capsular polysaccharides, and transferrin-binding proteins as well as several enzymes, ability of biofilm formation, etc., is more difficult, and it is impossible to evaluate the interaction of the different virulence factors and judge the virulence of A. pleuropneumoniae in vitro [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 51 ]. Laboratory rodents have been used as infection models, but their pathogenesis does not represent that in pigs [ 52 , 53 , 54 ].…”

“…Fimbria, outer membrane proteins, lipopolysaccharides, polysaccharides, ability of biofilm formation, presence of transporter systems, and different enzymes can also facilitate A. pleuropneumoniae in causing disease. The variety of the virulence factors results in great differences in the virulence of the strains [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Rhein kills Actinobacillus pleuropneumoniae, reduces biofilm formation, and effectively treats bacterial lung infections in mice

“…Actinobacillus pleuropneumoniae , a significant bacterial pathogen of the porcine respiratory tract, is responsible for causing pig pleuropneumonia, and has led to substantial economic losses globally [1]. A. pleuropneumoniae is a Gram-negative bacterium with a coccobacillary morphology.…”