The xaxAB Genes Encoding a New Apoptotic Toxin from the Insect Pathogen Xenorhabdus nematophila Are Present in Plant and Human Pathogens

ABSTRACT Bacteria-infecting viruses (phages) and their hosts maintain an ancient and complex relationship. Bacterial predation by lytic phages drives an ongoing phage-host arms race, whereas temperate phages initiate mutualistic relationships with their hosts upon lysogenization as prophages. In human pathogens, these prophages impact bacterial virulence in distinct ways: by secretion of phage-encoded toxins, modulation of the bacterial envelope, mediation of bacterial infectivity and the control of bacterial cell regulation. This review builds the argument that virulence-influencing prophages hold extensive, unexplored potential for biotechnology. More specifically, it highlights the development potential of novel therapies against infectious diseases, to address the current antibiotic resistance crisis. First, designer bacteriophages may serve to deliver genes encoding cargo proteins which repress bacterial virulence. Secondly, one may develop small molecules mimicking phage-derived proteins targeting central regulators of bacterial virulence. Thirdly, bacteria equipped with phage-derived synthetic circuits which modulate key virulence factors could serve as vaccine candidates to prevent bacterial infections. The development and exploitation of such antibacterial strategies will depend on the discovery of other prophage-derived, virulence control mechanisms and, more generally, on the dissection of the mutualistic relationship between temperate phages and bacteria, as well as on continuing developments in the synthetic biology field.

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Putative VanRS-Like Two-Component Regulatory System Associated with the Inducible Glycopeptide Resistance Cluster of Paenibacillus popilliae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.7.2625-2633.2005 ◽

2005 ◽

Vol 49 (7) ◽

pp. 2625-2633 ◽

Cited By ~ 12

Author(s):

Henry Fraimow ◽

Christopher Knob ◽

Inmaculada A. Herrero ◽

Robin Patel

Keyword(s):

Regulatory System ◽

Growth Curves ◽

Upstream Region ◽

Bacillus Halodurans ◽

Human Pathogens ◽

Glycopeptide Resistance ◽

Transposase Gene ◽

Two Component ◽

Genes Encoding ◽

Paenibacillus Lentimorbus

ABSTRACT Paenibacillus popilliae contains vanF encoding a putative d-Ala:d-lactate (d-Lac) ligase, VanF, as part of the vanY F Z F H F FX F cluster that is similar in structure to the enterococcal vanA and vanB clusters. Using growth curves, we demonstrated that vancomycin resistance in P. popilliae is inducible. Using degenerate oligonucleotides targeted at bacterial cell wall ligases, we identified a second ligase gene with features of a d-Ala:d-Ala ligase in both P. popilliae and the related, vancomycin-susceptible, Paenibacillus lentimorbus. The 3,380-bp region upstream of vanY F Z F H F FX F in P. popilliae ATCC 14706 was sequenced and found to contain genes encoding a putative two-component regulator, VanRFSF, similar to VanRS but more closely related to a family of two-component regulators linked to VanY-like carboxypeptidases in several glycopeptide-susceptible Bacillus species. This upstream region also included a transposase similar to a transposase found in Bacillus halodurans and, in some strains, a 99-bp insertion of unknown function with 95% nucleotide identity to a portion of the Tn1546 transposase gene. Analysis of glycopeptide resistance-associated clusters from soil and/or insect-dwelling organisms may provide important clues to the molecular evolution of acquired glycopeptide resistance elements in human pathogens.

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Studies on Bd0934 and Bd3507, Two Secreted Nucleases from Bdellovibrio bacteriovorus, Reveal Sequential Release of Nucleases during the Predatory Cycle

Journal of Bacteriology ◽

10.1128/jb.00150-20 ◽

2020 ◽

Vol 202 (18) ◽

Author(s):

Ewa Bukowska-Faniband ◽

Tilde Andersson ◽

Rolf Lood

Keyword(s):

Antibiotic Resistance ◽

Life Cycle ◽

Antibiotic Resistance Genes ◽

Human Pathogens ◽

Temporal Expression ◽

Bdellovibrio Bacteriovorus ◽

Exogenous Dna ◽

Content Type ◽

Genes Encoding ◽

Predatory Bacteria

ABSTRACT Bdellovibrio bacteriovorus is an obligate predatory bacterium that invades and kills a broad range of Gram-negative prey cells, including human pathogens. Its potential therapeutic application has been the subject of increased research interest in recent years. However, an improved understanding of the fundamental molecular aspects of the predatory life cycle is crucial for developing this bacterium as a “living antibiotic.” During intracellular growth, B. bacteriovorus secretes an arsenal of hydrolases, which digest the content of the host cell to provide growth nutrients for the predator, e.g., prey DNA is completely degraded by the nucleases. Here, we have, on a genetic and molecular level, characterized two secreted DNases from B. bacteriovorus, Bd0934 and Bd3507, and determined the temporal expression profile of other putative secreted nucleases. We conclude that Bd0934 and Bd3507 are likely a part of the predatosome but are not essential for the predation, host-independent growth, prey biofilm degradation, and self-biofilm formation. The detailed temporal expression analysis of genes encoding secreted nucleases revealed that these enzymes are produced in a sequential orchestrated manner. This work contributes to our understanding of the sequential breakdown of the prey nucleic acid by the nucleases secreted during the predatory life cycle of B. bacteriovorus. IMPORTANCE Antibiotic resistance is a major global concern with few available new means to combat it. From a therapeutic perspective, predatory bacteria constitute an interesting tool. They not only eliminate the pathogen but also reduce the overall pool of antibiotic resistance genes through secretion of nucleases and complete degradation of exogenous DNA. Molecular knowledge of how these secreted DNases act will give us further insight into how antibiotic resistance, and the spread thereof, can be limited through the action of predatory bacteria.

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Postgenomic Scan of Metallo-β-Lactamase Homologues in Rhizobacteria: Identification and Characterization of BJP-1, a Subclass B3 Ortholog from Bradyrhizobium japonicum

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01551-05 ◽

2006 ◽

Vol 50 (6) ◽

pp. 1973-1981 ◽

Cited By ~ 31

Author(s):

Magdalena Stoczko ◽

Jean-Marie Frère ◽

Gian Maria Rossolini ◽

Jean-Denis Docquier

Keyword(s):

Bradyrhizobium Japonicum ◽

Catalytic Efficiency ◽

Open Reading Frames ◽

Human Pathogens ◽

Microbial Genomes ◽

E Coli ◽

Genes Encoding ◽

And Function ◽

Identification And Characterization

ABSTRACT The diffusion of metallo-β-lactamases (MBLs) among clinically important human pathogens represents a therapeutic issue of increasing importance. However, the origin of these resistance determinants is largely unknown, although an important number of proteins belonging to the MBL superfamily have been identified in microbial genomes. In this work, we analyzed the distribution and function of genes encoding MBL-like proteins in the class Rhizobiales. Among 12 released complete genomes of members of the class Rhizobiales, a total of 57 open reading frames (ORFs) were found to have the MBL conserved motif and identity scores with MBLs ranging from 8 to 40%. On the basis of the best identity scores with known MBLs, four ORFs were cloned into Escherichia coli for heterologous expression. Among their products, one (blr6230) encoded by the Bradyrhizobium japonicum USDA110 genome, named BJP-1, hydrolyzed β-lactams when expressed in E. coli. BJP-1 enzyme is most closely related to the CAU-1 enzyme from Caulobacter vibrioides (40% amino acid sequence identity), a member of subclass B3 MBLs. A kinetic analysis revealed that BJP-1 efficiently hydrolyzed most β-lactam substrates, except aztreonam, ticarcillin, and temocillin, with the highest catalytic efficiency measured with meropenem. Compared to other MBLs, BJP-1 was less sensitive to inactivation by chelating agents.

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The Biopesticide Paenibacillus popilliae Has a Vancomycin Resistance Gene Cluster Homologous to the Enterococcal VanA Vancomycin Resistance Gene Cluster

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.44.3.705-709.2000 ◽

2000 ◽

Vol 44 (3) ◽

pp. 705-709 ◽

Cited By ~ 60

Author(s):

Robin Patel ◽

Kerryl Piper ◽

Franklin R. Cockerill ◽

James M. Steckelberg ◽

Allan A. Yousten

Keyword(s):

Gene Cluster ◽

Resistance Gene ◽

Bacterial Resistance ◽

Vancomycin Resistance ◽

Amino Acid Sequences ◽

Agricultural Practice ◽

Human Pathogens ◽

Resistance Gene Cluster ◽

Genes Encoding ◽

Vancomycin Resistant

ABSTRACT We have previously identified, in Paenibacillus popilliae, a 708-bp sequence which has homology to the sequence of the enterococcal vanA gene. We have performed further studies revealing five genes encoding homologues of VanY, VanZ, VanH, VanA, and VanX in P. popilliae. The predicted amino acid sequences are similar to those in VanA vancomycin-resistant enterococci: 61% identity for VanY, 21% for VanZ, 74% for VanH, 77% for VanA, and 79% for VanX. The genes in P. popilliae may have been a precursor to or have had ancestral genes in common with vancomycin resistance genes in enterococci. The use of P. popilliae biopesticidal preparations in agricultural practice may have an impact on bacterial resistance in human pathogens.

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Virulence and Pathogen Multiplication: A Serial Passage Experiment in the Hypervirulent Bacterial Insect-Pathogen Xenorhabdus nematophila

PLoS ONE ◽

10.1371/journal.pone.0015872 ◽

2011 ◽

Vol 6 (1) ◽

pp. e15872 ◽

Cited By ~ 9

Author(s):

Élodie Chapuis ◽

Sylvie Pagès ◽

Vanya Emelianoff ◽

Alain Givaudan ◽

Jean-Baptiste Ferdy

Keyword(s):

Serial Passage ◽

Xenorhabdus Nematophila ◽

Insect Pathogen

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Trade-offs shape the evolution of the vector-borne insect pathogen Xenorhabdus nematophila

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2012.0228 ◽

2012 ◽

Vol 279 (1738) ◽

pp. 2672-2680 ◽

Cited By ~ 18

Author(s):

Élodie Chapuis ◽

Audrey Arnal ◽

Jean-Baptiste Ferdy

Keyword(s):

Xenorhabdus Nematophila ◽

Insect Pathogen ◽

Trade Offs ◽

Vector Borne

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Salivaricin D, a Novel Intrinsically Trypsin-Resistant Lantibiotic from Streptococcus salivarius 5M6c Isolated from a Healthy Infant

Applied and Environmental Microbiology ◽

10.1128/aem.06588-11 ◽

2011 ◽

Vol 78 (2) ◽

pp. 402-410 ◽

Cited By ~ 39

Author(s):

Dagim Jirata Birri ◽

Dag Anders Brede ◽

Ingolf F. Nes

Keyword(s):

Abc Transporters ◽

Response Regulator ◽

Probiotic Bacterium ◽

Streptococcus Salivarius ◽

Human Pathogens ◽

Gene Encoding ◽

Content Type ◽

Gram Positive Bacteria ◽

Genes Encoding ◽

Immunity Function

ABSTRACTIn this work, we purified and characterized a newly identified lantibiotic (salivaricin D) fromStreptococcus salivarius5M6c. Salivaricin D is a 34-amino-acid-residue peptide (3,467.55 Da); the locus of the gene encoding this peptide is a 16.5-kb DNA segment which contains genes encoding the precursor of two lantibiotics, two modification enzymes (dehydratase and cyclase), an ABC transporter, a serine-like protease, immunity proteins (lipoprotein and ABC transporters), a response regulator, and a sensor histidine kinase. The immunity gene (salI) was heterologously expressed in a sensitive indicator and provided significant protection against salivaricin D, confirming its immunity function. Salivaricin D is a naturally trypsin-resistant lantibiotic that is similar to nisin-like lantibiotics. It is a relatively broad-spectrum bacteriocin that inhibits members of many genera of Gram-positive bacteria, including the important human pathogensStreptococcus pyogenesandStreptococcus pneumoniae. Thus,Streptococcus salivarius5M6c may be a potential biological agent for the control of oronasopharynx-colonizing streptococcal pathogens or may be used as a probiotic bacterium.

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GENERAL PRINCIPLES OF ANTIBIOTIC RESISTANCE EVOLUTION IN BACTERIA (REVIEW OF LITERATURE)

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2020-65-6-387-393 ◽

2020 ◽

Vol 65 (6) ◽

pp. 387-393

Author(s):

N. V. Davidovich ◽

Natalya Nilolaevna Kukalevskaya ◽

E. N. Bashilova ◽

T. A. Bazhukova

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Molecular Genetic ◽

Antibiotic Resistance Genes ◽

Human Pathogens ◽

Intrinsic Resistance ◽

Resistance Evolution ◽

Genes Encoding ◽

The Impact

Currently, the impact of antibiotic resistance on human health is a worldwide problem and its study is of great interest from a molecular genetic, environmental and clinical view-point. This review summarizes the latest data about antibiotic resistance, the classification of microorganisms as sensitive and resistant to the action of antibiotics, reveals the concept of minimum inhibitory concentration from modern positions. The resistance of microorganisms to antibacterial agents can be intrinsic and acquired, as well as being one of the examples of evolution that are currently available for study. Modern methods of whole-genome sequencing and complex databases of nucleotide-tagged libraries give an idea of the multifaceted nature of the mechanisms of intrinsic resistance to antibiotics and are able to provide information on genes encoding metabolic enzymes and proteins that regulate the basic processes of the physiology of bacteria. The article describes the main ways of spreading the resistance of microorganisms, reflects the concepts of “founder effect” and the fitness cost of bacteria, which underlie the emergence and evolution of antibiotic resistance. It is shown that the origin of antibiotic resistance genes that human pathogens currently possess can be traced by studying the surrounding not only clinical, but also non-clinical (ecological) habitats. As well as microorganisms of the surrounding ecosystems are the donors of resistance genes in horizontal gene transfer.

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A Conserved α-Helix Essential for a Type VI Secretion-Like System of Francisella tularensis

Journal of Bacteriology ◽

10.1128/jb.01759-08 ◽

2009 ◽

Vol 191 (8) ◽

pp. 2431-2446 ◽

Cited By ~ 62

Author(s):

Jeanette E. Bröms ◽

Moa Lavander ◽

Anders Sjöstedt

Keyword(s):

Complex Formation ◽

Francisella Tularensis ◽

Yersinia Pseudotuberculosis ◽

Point Mutations ◽

Human Pathogens ◽

Type Vi Secretion System ◽

Type Vi Secretion ◽

Serovar Typhimurium ◽

Genes Encoding ◽

Α Helix

ABSTRACT Francisella tularensis harbors genes with similarity to genes encoding components of a type VI secretion system (T6SS) recently identified in several gram-negative bacteria. These genes include iglA and iglB encoding IglA and IglB, homologues of which are conserved in most T6SSs. We used a yeast two-hybrid system to study the interaction of the Igl proteins of F. tularensis LVS. We identified a region of IglA, encompassing residues 33 to 132, necessary for efficient binding to IglB, as well as for IglAB protein stability and intramacrophage growth. In particular, residues 103 to 122, overlapping a highly conserved α-helix, played an absolutely essential role. Point mutations within this domain caused modest defects in IglA-IglB binding in the yeast Saccharomyces cerevisiae but markedly impaired intramacrophage replication and phagosomal escape, resulting in severe attenuation of LVS in mice. Thus, IglA-IglB complex formation is clearly crucial for Francisella pathogenicity. This interaction may be universal to type VI secretion, since IglAB homologues of Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Vibrio cholerae, Salmonella enterica serovar Typhimurium, and Escherichia coli were also shown to interact in yeast, and the interaction was dependent on preservation of the same α-helix. Heterologous interactions between nonnative IglAB proteins further supported the notion of a conserved binding site. Thus, IglA-IglB complex formation is clearly crucial for Francisella pathogenicity, and the same interaction is conserved in other human pathogens.

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