scholarly journals Role of Teichoic Acid Choline Moieties in the Virulence of Streptococcus pneumoniae

2009 ◽  
Vol 77 (7) ◽  
pp. 2824-2831 ◽  
Author(s):  
Florian Gehre ◽  
Radek Spisek ◽  
Arun S. Kharat ◽  
Phillip Matthews ◽  
Anjli Kukreja ◽  
...  

ABSTRACT In recent reports it was shown that genetically modified choline-free strains of Streptococcus pneumoniae (D39Cho−licA64 and D39ChiplicB31) expressing the type II capsular polysaccharide were virtually avirulent in the murine sepsis model, in sharp contrast to the isogenic and highly virulent strains D39Cho− and D39Chip, which have retained the choline residues at their surface. We now demonstrate that this choline-associated virulence is independent of Toll-like receptor 2 recognition. Also, despite the lack of virulence, choline-free strains of S. pneumoniae were able to activate splenic dendritic cells, induce secretion of proinflammatory cytokines, and produce specific protective immunity against subsequent challenge. However, after this transient engagement of the immune system the choline-free bacteria were rapidly cleared from the blood, while the isogenic virulent strain D39Cho− continued to grow, accompanied by prolonged expression of cytokines, eventually killing the experimental animals. The critical contribution of choline residues to the virulence potential of pneumococci appears to be the role that these amino alcohol residues play in a pneumococcal immune evasion strategy, the mechanism of which is unknown at the present time.

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Lukas Schuwerk ◽  
Doris Hoeltig ◽  
Karl-Heinz Waldmann ◽  
Peter Valentin-Weigand ◽  
Judith Rohde

AbstractSerotyping is the most common method to characterize field isolates of Actinobacillus (A.) pleuropneumoniae, the etiological agent of porcine pleuropneumonia. Based on serology, many farms seem to be infected and antibodies against a wide variety of serovars are detectable, but, so far it is unknown to what degree respective serovars contribute to outbreaks of clinical manifest disease. In this study, 213 German A. pleuropneumoniae field isolates retrieved for diagnostic purposes from outbreaks of porcine pleuropneumonia between 2010 and 2019 were genetically serotyped and analyzed regarding their apx-toxin gene profile using molecular methods. Serotyping revealed a prominent role of serovar 2 in clinical cases (64% of all isolates) and an increase in the detection of this serovar since 2010 in German isolates. Serovar 9/11 followed as the second most frequent serovar with about 15% of the isolates. Furthermore, very recently described serovars 16 (n = 2) and 18 (n = 8) were detected. Most isolates (93.4%) showed apx-profiles typical for the respective serovar. However, this does not hold true for isolates of serovar 18, as 75% (n = 6) of all isolates of this serovar deviated uniformly from the “typical” apx-gene profile of the reference strain 7311555. Notably, isolates from systemic lesions such as joints or meninges did not harbor the complete apxICABD operon which is considered typical for highly virulent strains. Furthermore, the extremely low occurrence (n = 1) of NAD independent (biovar II) isolates in German A. pleuropneumoniae was evident in our collection of clinical isolates.


2009 ◽  
Vol 77 (7) ◽  
pp. 3100-3108 ◽  
Author(s):  
Fengchan Han ◽  
Heping Yu ◽  
Cong Tian ◽  
Shengli Li ◽  
Michael R. Jacobs ◽  
...  

ABSTRACT Streptococcus pneumoniae is the most common pathogen associated with otitis media. To examine the role of Toll-like receptor 2 (TLR2) in host defense against Streptococcus pneumoniae infection in the middle ear, wild-type (WT; C57BL/6) and TLR2-deficient (TLR2−/−) mice were inoculated with Streptococcus pneumoniae (1 × 106 CFU) through the tympanic membrane. Nineteen of 37 TLR2−/− mice showed bacteremia and died within 3 days after the challenge, compared to only 4 of 32 WT mice that died. Of those that survived, more severe hearing loss in the TLR2−/− mice than in the WT mice was indicated by an elevation in auditory-evoked brain stem response thresholds at 3 or 7 days postinoculation. The histological pathology was characterized by effusion and tissue damage in the middle ear, and in the TLR2−/− mice, the outcome of infection became more severe at 7 days. At both 3 and 7 days postchallenge, the TLR2−/− mice had higher blood bacterial titers than the WT mice (P < 0.05), and typical bacteria were identified in the effusion from both ears of both mouse groups by acridine orange staining. Moreover, by 3 days postchallenge, the mRNA accumulation levels of NF-κB, tumor necrosis factor alpha, interleukin 1β, MIP1α, Muc5ac, and Muc5b were significantly lower in the ears of TLR2−/− mice than in WT mice. In summary, TLR2−/− mice may produce relatively low levels of proinflammatory cytokines following pneumococcal challenge, thus hindering the clearance of bacteria from the middle ear and leading to sepsis and a high mortality rate. This study provides evidence that TLR2 is important in the molecular pathogenesis and host response to otitis media.


PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0190402 ◽  
Author(s):  
Zuleeza Ahmad ◽  
Richard M. Harvey ◽  
James C. Paton ◽  
Alistair J. Standish ◽  
Renato Morona

HortScience ◽  
2009 ◽  
Vol 44 (7) ◽  
pp. 2038-2040 ◽  
Author(s):  
Yutaka Mimura ◽  
Masami Yoshikawa ◽  
Masashi Hirai

Bacterial wilt caused by Ralstonia solanacearum is one of the most serious diseases in pepper (Capsicum annuum) crops in warm-temperate, subtropical, and tropical areas, including Japan. Resistant lines are a prerequisite for breeding resistant cultivars but are not well studied. Eight pepper accessions previously described as resistant to the pathogen were selected and inoculated with a highly virulent strain, KP9547. Among them, Malaysian accession LS2341 exhibited the highest resistance. Accession LS2341 was then challenged with 14 virulent strains collected from various areas in Japan. The strains cover biovars 2T, 3, and 4 and include isolates from the host plants of tomato, eggplant, and pepper. Results indicated that accession LS2341 had the highest level of resistance to all the strains of R. solanacearum examined. Therefore, accession LS2341 was confirmed as an appropriate source for the breeding of resistant cultivars of pepper in Japan and is a candidate for a potential source of resistance in other areas.


2015 ◽  
Vol 83 (5) ◽  
pp. 1957-1972 ◽  
Author(s):  
Zhensong Wen ◽  
Odeniel Sertil ◽  
Yongxin Cheng ◽  
Shanshan Zhang ◽  
Xue Liu ◽  
...  

Streptococcus pneumoniaeis a major bacterial pathogen in humans. Its polysaccharide capsule is a key virulence factor that promotes bacterial evasion of human phagocytic killing. WhileS. pneumoniaeproduces at least 94 antigenically different types of capsule, the genes for biosynthesis of almost all capsular types are arranged in the same locus. The transcription of the capsular polysaccharide (cps) locus is not well understood. This study determined the transcriptional features of thecpslocus in the type 2 virulent strain D39. The initial analysis revealed that thecpsgenes are cotranscribed from a major transcription start site at the −25 nucleotide (G) upstream ofcps2A, the first gene in the locus. Using unmarked chromosomal truncations and a luciferase-based transcriptional reporter, we showed that the full transcription of thecpsgenes not only depends on the core promoter immediately upstream ofcps2A, but also requires additional elements upstream of the core promoter, particularly a 59-bp sequence immediately upstream of the core promoter. Unmarked deletions of these promoter elements in the D39 genome also led to significant reduction in CPS production and virulence in mice. Lastly, commoncpsgene (cps2ABCD) mutants did not show significant abnormality incpstranscription, although they produced significantly less CPS, indicating that the CpsABCD proteins are involved in the encapsulation ofS. pneumoniaein a posttranscriptional manner. This study has yielded important information on the transcriptional characteristics of thecpslocus inS. pneumoniae.


2020 ◽  
Vol 12 (2) ◽  
pp. 3951-3956
Author(s):  
Amandeep Kaur ◽  
Kanika Bansal ◽  
Prabhu B Patil

Abstract Xanthomonas oryzae pv. oryzae (Xoo) is a serious pathogen of rice which displays tremendous interstrain variation. The emergence of highly-virulent strains of Xoo is a major threat to rice cultivation. Evolutionary insights into genome dynamics of highly virulent strains as compared with the less-virulent ones are crucial for understanding the molecular basis of exceptional success of Xoo as a highly evolved plant pathogen. In the present study, we report complete genome sequence of Xoo strains with extreme-virulent pathotypes (XVPs) characterized based on their reaction toward ten resistance (Xa) genes. One strain, IXO1088, can overcome resistance mediated by all the ten resistance genes while the other strain IXO704 cannot overcome any of them. Interestingly, our investigation revealed that XVPs display dramatic variation in the genome structure with numerous rearrangements/inversions. Moreover, XVPs also possess distinct transposon content and prophage elements that may provide genomic flux required for the acquisition of novel gene cassettes and structural changes in the genome. Interestingly, analysis of transcription activator-like effector proteins, which are major virulence determinants of Xanthomonas pathogen show marked variation in the transcription activator-like effector content and DNA binding domain of tal genes. Overall, the present study indicates the possible role of mobilomes and repetitive elements in major structural and sequence alterations, which may be leading to the emergence of novel and extreme pathotypes. The knowledge and resource of XVPs will be invaluable in the further systematic understanding of evolution and management of variant pathotypes of Xoo.


2008 ◽  
Vol 191 (4) ◽  
pp. 1200-1210 ◽  
Author(s):  
Stefanie Baur ◽  
Jon Marles-Wright ◽  
Stephan Buckenmaier ◽  
Richard J. Lewis ◽  
Waldemar Vollmer

ABSTRACT Streptococcus pneumoniae has unusually complex cell wall teichoic acid and lipoteichoic acid, both of which contain a ribitol phosphate moiety. The lic region of the pneumococcal genome contains genes for the uptake and activation of choline, the attachment of phosphorylcholine to teichoic acid precursors, and the transport of these precursors across the cytoplasmic membrane. The role of two other, so far uncharacterized, genes, spr1148 and spr1149, in the lic region was determined. TarJ (spr1148) encodes an NADPH-dependent alcohol dehydrogenase for the synthesis of ribitol 5-phosphate from ribulose 5-phosphate. TarI (spr1149) encodes a cytidylyl transferase for the synthesis of cytidine 5′-diphosphate (CDP)-ribitol from ribitol 5-phosphate and cytidine 5′-triphosphate. We also present the crystal structure of TarI with and without bound CDP, and the structures present a rationale for the substrate specificity of this key enzyme. No transformants were obtained with insertion plasmids designed to interrupt the tarIJ genes, indicating that their function could be essential for cell growth. CDP-activated ribitol is a precursor for the synthesis of pneumococcal teichoic acids and some of the capsular polysaccharides. Thus, all eight genes in the lic region have a role in teichoic acid synthesis.


2018 ◽  
Vol 86 (3) ◽  
Author(s):  
Shigeto Hamaguchi ◽  
M. Ammar Zafar ◽  
Michael Cammer ◽  
Jeffrey N. Weiser

ABSTRACT Person-to-person transmission of Streptococcus pneumoniae (the pneumococcus) may occur via environmental sources in close contact with carriers. Pneumococcal polysaccharide capsules, the determinant of serotype (or type), are heterogeneous in structure and amount, and these differences affect rates of transmission. In this study, we examined the contribution of capsule and its variations to the maintenance of pneumococcal viability under starvation conditions. S. pneumoniae retained its ability to colonize infant mice even after incubation for 24 h in phosphate-buffered saline at 25°C. The expression of capsule by the cps locus prolonged survival under these and other nutrient-poor conditions. Analysis of capsule-switch constructs showed that strain-to-strain differences in survival were due to capsule type rather than genetic background. The addition of glucose was sufficient to rescue the survival defect of the capsule-deficient derivative, demonstrating that in the absence of capsule, survival depends upon nutrient availability. During starvation, there was a decrease in capsule size and amount of capsular polysaccharide that was dependent on bacterial viability and the presence of the cps locus. These observations suggest that pneumococci catabolize their own capsular polysaccharide using the genes involved in its biosynthesis to maintain viability when other carbon sources are unavailable. Our findings describe a new role of the pneumococcal capsule: the prolongation of viability under nutrient-limiting conditions as would be encountered during periods when the organism is between hosts.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong Hu ◽  
Shiming Fu ◽  
Geng Zou ◽  
Anusak Kerdsin ◽  
Xiabing Chen ◽  
...  

AbstractStreptococcus suis has been well-recognized as a zoonotic pathogen worldwide, and the diversity and unpredictable adaptive potential of sporadic human strains represent a great risk to the public health. In this study, S. suis LSM178, isolated from a patient in contact with pigs and raw pork, was assessed as a hyper-virulent strain and interpreted for the virulence based on its genetic information. The strain was more invasive for Caco-2 cells than two other S. suis strains, SC19 and P1/7. Sequence analysis designated LSM178 with serotype 2 and a novel sequence type 1005. Phylogenetic analysis showed that LSM178 clustered with highly virulent strains including all human strains and epidemic strains. Compared with other strains, these S. suis have the most and the same virulent factors and a type I-89 K pathogenicity island. Further, groups of genes were identified to distinguish these highly virulent strains from other generally virulent strains, emphasizing the key roles of genes modeling transcription, cell barrier, replication, recombination and repair on virulence regulation. Additionally, LSM178 contains a novel prophage conducive potentially to pathogenicity.


2008 ◽  
Vol 190 (21) ◽  
pp. 7130-7140 ◽  
Author(s):  
Scott E. Battle ◽  
Folker Meyer ◽  
Jordi Rello ◽  
Vanderlene L. Kung ◽  
Alan R. Hauser

ABSTRACT Most known virulence determinants of Pseudomonas aeruginosa are remarkably conserved in this bacterium's core genome, yet individual strains differ significantly in virulence. One explanation for this discrepancy is that pathogenicity islands, regions of DNA found in some strains but not in others, contribute to the overall virulence of P. aeruginosa. Here we employed a strategy in which the virulence of a panel of P. aeruginosa isolates was tested in mouse and plant models of disease, and a highly virulent isolate, PSE9, was chosen for comparison by subtractive hybridization to a less virulent strain, PAO1. The resulting subtractive hybridization sequences were used as tags to identify genomic islands found in PSE9 but absent in PAO1. One 99-kb island, designated P. aeruginosa genomic island 5 (PAGI-5), was a hybrid of the known P. aeruginosa island PAPI-1 and novel sequences. Whereas the PAPI-1-like sequences were found in most tested isolates, the novel sequences were found only in the most virulent isolates. Deletional analysis confirmed that some of these novel sequences contributed to the highly virulent phenotype of PSE9. These results indicate that targeting highly virulent strains of P. aeruginosa may be a useful strategy for identifying pathogenicity islands and novel virulence determinants.


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