scholarly journals Comparative Genomics of Bacillus thuringiensis Reveals a Path to Specialized Exploitation of Multiple Invertebrate Hosts

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Jinshui Zheng ◽  
Qiuling Gao ◽  
Linlin Liu ◽  
Hualin Liu ◽  
Yueying Wang ◽  
...  

ABSTRACT Understanding the genetic basis of host shifts is a key genomic question for pathogen and parasite biology. The Bacillus cereus group, which encompasses Bacillus thuringiensis and Bacillus anthracis, contains pathogens that can infect insects, nematodes, and vertebrates. Since the target range of the essential virulence factors (Cry toxins) and many isolates is well known, this group presents a powerful system for investigating how pathogens can diversify and adapt to phylogenetically distant hosts. Specialization to exploit insects occurs at the level of the major clade and is associated with substantial changes in the core genome, and host switching between insect orders has occurred repeatedly within subclades. The transfer of plasmids with linked cry genes may account for much of the adaptation to particular insect orders, and network analysis implies that host specialization has produced strong associations between key toxin genes with similar targets. Analysis of the distribution of plasmid minireplicons shows that plasmids with orf156 and orf157, which carry genes encoding toxins against Lepidoptera or Diptera, were contained only by B. thuringiensis in the specialized insect clade (clade 2), indicating that tight genome/plasmid associations have been important in adaptation to invertebrate hosts. Moreover, the accumulation of multiple virulence factors on transposable elements suggests that cotransfer of diverse virulence factors is advantageous in terms of expanding the insecticidal spectrum, overcoming insect resistance, or through gains in pathogenicity via synergistic interactions between toxins. IMPORTANCE Population genomics have provided many new insights into the formation, evolution, and dynamics of bacterial pathogens of humans and other higher animals, but these pathogens usually have very narrow host ranges. As a pathogen of insects and nematodes, Bacillus thuringiensis, which produces toxins showing toxicity to many orders of insects and other invertebrates, can be used as a model to study the evolution of pathogens with wide host ranges. Phylogenomic analysis revealed that host specialization and switching occur at the level of the major clade and subclade, respectively. A toxin gene co-occurrence network indicates that multiple toxins with similar targets were accumulated by the same cell in the whole species. This accumulation may be one of the strategies that B. thuringiensis has used to fight against host resistance. This kind of formation and evolution of pathogens represents a different path used against multiple invertebrate hosts from that used against higher animals. IMPORTANCE Population genomics have provided many new insights into the formation, evolution, and dynamics of bacterial pathogens of humans and other higher animals, but these pathogens usually have very narrow host ranges. As a pathogen of insects and nematodes, Bacillus thuringiensis, which produces toxins showing toxicity to many orders of insects and other invertebrates, can be used as a model to study the evolution of pathogens with wide host ranges. Phylogenomic analysis revealed that host specialization and switching occur at the level of the major clade and subclade, respectively. A toxin gene co-occurrence network indicates that multiple toxins with similar targets were accumulated by the same cell in the whole species. This accumulation may be one of the strategies that B. thuringiensis has used to fight against host resistance. This kind of formation and evolution of pathogens represents a different path used against multiple invertebrate hosts from that used against higher animals.

2019 ◽  
Vol 11 (3) ◽  
pp. 954-969 ◽  
Author(s):  
Yann Dussert ◽  
Isabelle D Mazet ◽  
Carole Couture ◽  
Jérôme Gouzy ◽  
Marie-Christine Piron ◽  
...  

Abstract Downy mildews are obligate biotrophic oomycete pathogens that cause devastating plant diseases on economically important crops. Plasmopara viticola is the causal agent of grapevine downy mildew, a major disease in vineyards worldwide. We sequenced the genome of Pl. viticola with PacBio long reads and obtained a new 92.94 Mb assembly with high contiguity (359 scaffolds for a N50 of 706.5 kb) due to a better resolution of repeat regions. This assembly presented a high level of gene completeness, recovering 1,592 genes encoding secreted proteins involved in plant–pathogen interactions. Plasmopara viticola had a two-speed genome architecture, with secreted protein-encoding genes preferentially located in gene-sparse, repeat-rich regions and evolving rapidly, as indicated by pairwise dN/dS values. We also used short reads to assemble the genome of Plasmopara muralis, a closely related species infecting grape ivy (Parthenocissus tricuspidata). The lineage-specific proteins identified by comparative genomics analysis included a large proportion of RxLR cytoplasmic effectors and, more generally, genes with high dN/dS values. We identified 270 candidate genes under positive selection, including several genes encoding transporters and components of the RNA machinery potentially involved in host specialization. Finally, the Pl. viticola genome assembly generated here will allow the development of robust population genomics approaches for investigating the mechanisms involved in adaptation to biotic and abiotic selective pressures in this species.


2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Ahmad-Kamal Ghazali ◽  
Su-Anne Eng ◽  
Jia-Shiun Khoo ◽  
Seddon Teoh ◽  
Chee-Choong Hoh ◽  
...  

Burkholderia pseudomallei , a soil-dwelling Gram-negative bacterium, is the causative agent of the endemic tropical disease melioidosis. Clinical manifestations of B. pseudomallei infection range from acute or chronic localized infection in a single organ to fulminant septicaemia in multiple organs. The diverse clinical manifestations are attributed to various factors, including the genome plasticity across B. pseudomallei strains. We previously characterized B. pseudomallei strains isolated in Malaysia and noted different levels of virulence in model hosts. We hypothesized that the difference in virulence might be a result of variance at the genome level. In this study, we sequenced and assembled four Malaysian clinical B. pseudomallei isolates, UKMR15, UKMPMC2000, UKMD286 and UKMH10. Phylogenomic analysis showed that Malaysian subclades emerged from the Asian subclade, suggesting that the Malaysian strains originated from the Asian region. Interestingly, the low-virulence strain, UKMH10, was the most distantly related compared to the other Malaysian isolates. Genomic island (GI) prediction analysis identified a new island of 23 kb, GI9c, which is present in B. pseudomallei and Burkholderia mallei , but not Burkholderia thailandensis . Genes encoding known B. pseudomallei virulence factors were present across all four genomes, but comparative analysis of the total gene content across the Malaysian strains identified 104 genes that are absent in UKMH10. We propose that these genes may encode novel virulence factors, which may explain the reduced virulence of this strain. Further investigation on the identity and role of these 104 proteins may aid in understanding B. pseudomallei pathogenicity to guide the design of new therapeutics for treating melioidosis.


PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e27387 ◽  
Author(s):  
Neil Fernandes ◽  
Rebecca J. Case ◽  
Sharon R. Longford ◽  
Mohammad R. Seyedsayamdost ◽  
Peter D. Steinberg ◽  
...  

2015 ◽  
Vol 81 (6) ◽  
pp. 1909-1918 ◽  
Author(s):  
Daniela Ceccarelli ◽  
Arlene Chen ◽  
Nur A. Hasan ◽  
Shah M. Rashed ◽  
Anwar Huq ◽  
...  

ABSTRACTNon-O1/non-O139Vibrio choleraeinhabits estuarine and coastal waters globally, but its clinical significance has not been sufficiently investigated, despite the fact that it has been associated with septicemia and gastroenteritis. The emergence of virulent non-O1/non-O139V. choleraeis consistent with the recognition of new pathogenic variants worldwide. Oyster, sediment, and water samples were collected during a vibrio surveillance program carried out from 2009 to 2012 in the Chesapeake Bay, Maryland.V. choleraeO1 was detected by a direct fluorescent-antibody (DFA) assay but was not successfully cultured, whereas 395 isolates of non-O1/non-O139V. choleraewere confirmed by multiplex PCR and serology. Only a few of the non-O1/non-O139V. choleraeisolates were resistant to ampicillin and/or penicillin. Most of the isolates were sensitive to all antibiotics tested, and 77 to 90% carried the El Tor variant hemolysin genehlyAET, the actin cross-linking repeats in toxin genertxA, the hemagglutinin protease genehap, and the type 6 secretion system. About 19 to 21% of the isolates carried the neuraminidase-encoding genenanHand/or the heat-stable toxin (NAG-ST), and only 5% contained a type 3 secretion system. None of the non-O1/non-O139V. choleraeisolates containedVibriopathogenicity island-associated genes. However,ctxA,ace, orzotwas present in nine isolates. Fifty-five different genotypes showed up to 12 virulence factors, independent of the source of isolation, and represent the first report of both antibiotic susceptibility and virulence associated with non-O1/non-O139V. choleraefrom the Chesapeake Bay. Since these results confirm the presence of potentially pathogenic non-O1/non-O139V. cholerae, monitoring for totalV. cholerae, regardless of serotype, should be done within the context of public health.


2005 ◽  
Vol 71 (12) ◽  
pp. 8107-8114 ◽  
Author(s):  
Viviane Zahner ◽  
Diana Aparecida Cabral ◽  
Adriana Hamond Régua-Mangia ◽  
Leon Rabinovitch ◽  
Gaétan Moreau ◽  
...  

ABSTRACT One hundred twenty-one strains of the Bacillus cereus complex, of which 80 were isolated from a variety of sources in Brazil, were screened by PCR for the presence of sequences (bceT, hblA, nheBC, plc, sph, and vip3A) encoding putative virulence factors and for polymorphisms in variable-number tandem repeats (VNTR), using a variable region of the vrrA open reading frame as the target. Amplicons were generated from isolates of B. cereus and Bacillus thuringiensis for each of the sequences encoding factors suggested to play a role in infections of mammals. Intriguingly, the majority of these sequences were detected more frequently in Bacillus thuringiensis than in B. cereus. The vip3A sequence, which encodes an insecticidal toxin, was detected exclusively in B. thuringiensis. VNTR analysis demonstrated the presence of five different fragment length categories in both species, with two of these being widely distributed throughout both taxa. In common with data generated from previous studies examining European, Asian, or North American populations, our investigation of Brazilian isolates supports the notion that B. cereus and B. thuringiensis should be considered to represent a single species.


mBio ◽  
2010 ◽  
Vol 1 (3) ◽  
Author(s):  
Alexandra Grubman ◽  
Alexandra Phillips ◽  
Marie Thibonnier ◽  
Maria Kaparakis-Liaskos ◽  
Chad Johnson ◽  
...  

ABSTRACTDespite recent advances in our understanding of howHelicobacter pyloricauses disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors inH. pylori, we generated low-infectivity variants of a mouse-colonizingH. pyloristrain using the classical technique ofin vitroattenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of theEscherichia colivitamin B6biosynthesis enzymes PdxA and PdxJ. Functional complementation studies withE. coliconfirmedH. pyloriPdxA and PdxJ to bebona fidehomologs of vitamin B6biosynthesis enzymes. Importantly,H. pyloriPdxA was required for optimal growthin vitroand was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B6is necessary for the synthesis of glycosylated flagella and for flagellum-based motility inH. pylori. Thus, for the first time, we identify vitamin B6biosynthesis enzymes as novel virulence factors in bacteria. Interestingly,pdxAandpdxJorthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.IMPORTANCEApproximately half of the world’s population is infected withH. pylori, yet howH. pyloribacteria establish chronic infections in human hosts remains elusive. From gene array studies, we identified two genes as representing potentially novel colonization factors forH. pylori. These genes encoded enzymes involved in the synthesis of vitamin B6, an important molecule for many metabolic reactions in living organisms. Little is currently known regarding vitamin B6biosynthesis in human pathogens. We showed that mutantH. pyloribacteria lacking an enzyme involved inde novovitamin B6biosynthesis, PdxA, were unable to synthesize motility appendages (flagella) and were unable to establish chronic colonization in mice. Thus, this work identifies vitamin B6biosynthesis enzymes as novel virulence factors for bacterial pathogens. Interestingly, a number of human pathogens, but not their mammalian hosts, possess these genes, which suggests that Pdx enzymes may represent ideal candidates for new therapeutic targets.


2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Ponnerassery S. Sudheesh ◽  
Aliya Al-Ghabshi ◽  
Nashwa Al-Mazrooei ◽  
Saoud Al-Habsi

Fish living in the wild as well as reared in the aquaculture facilities are susceptible to infectious diseases caused by a phylogenetically diverse collection of bacterial pathogens. Control and treatment options using vaccines and drugs are either inadequate, inefficient, or impracticable. The classical approach in studying fish bacterial pathogens has been looking at individual or few virulence factors. Recently, genome sequencing of a number of bacterial fish pathogens has tremendously increased our understanding of the biology, host adaptation, and virulence factors of these important pathogens. This paper attempts to compile the scattered literature on genome sequence information of fish pathogenic bacteria published and available to date. The genome sequencing has uncovered several complex adaptive evolutionary strategies mediated by horizontal gene transfer, insertion sequence elements, mutations and prophage sequences operating in fish pathogens, and how their genomes evolved from generalist environmental strains to highly virulent obligatory pathogens. In addition, the comparative genomics has allowed the identification of unique pathogen-specific gene clusters. The paper focuses on the comparative analysis of the virulogenomes of important fish bacterial pathogens, and the genes involved in their evolutionary adaptation to different ecological niches. The paper also proposes some new directions on finding novel vaccine and chemotherapeutic targets in the genomes of bacterial pathogens of fish.


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