Source: CONNECTICUT AGRICULTURAL EXPERIMENT STATION submitted to
MOLECULAR BIOLOGICAL CHARACTERIZATION OF THE PAENIBACILLUS POPILLIAE GENOME
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
TERMINATED
Funding Source
Reporting Frequency
Annual
Accession No.
0198426
Grant No.
(N/A)
Project No.
CONH00243
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Oct 1, 2003
Project End Date
Sep 30, 2006
Grant Year
(N/A)
Project Director
Dingman, D. W.
Recipient Organization
CONNECTICUT AGRICULTURAL EXPERIMENT STATION
PO BOX 1106
NEW HAVEN,CT 06504
Performing Department
BIOCHEMISTRY & GENETICS
Non Technical Summary
The need for "natural alternatives" to replace synthetic pesticides requires research investigations on biological controls. For maximum exploitation, molecular biological characterizations of these biological control agents are needed. This project seeks to provide a foundational map of the P. popilliae chromsome and to produce a library of chromsomal fragments from which to readily obtain genes of interest. This library will be aligned with the chromsomal map and a system for identifying and isolating genes will be tested.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
2154010104060%
2154010110030%
2154010116010%
Goals / Objectives
The larval and adult stages of scarab beetles (order Coleoptera, family Scarabaeidae) cause considerable economic losses to agricultural and horticultural industries. Two decades ago, the annual damage to turfgrass in the U. S. was estimated to be one-quarter of a billion dollars. No estimate has been made on the economic loss these insects have also caused to ornamental plantings, fruit production, and other segments of agriculture. At present, the only effective control for scarab beetles is the use of synthetic insecticides. However, public worries about the health and environmental hazards associated with the use of these chemicals have increased the demand for the development of safer biological alternatives. Many synthetic pesticides are being, or have been, banded or greatly restricted from use without a good biocontrol replacement. Considerable attention is being focused on the development and use of biological control agents as "natural alternatives" to replace synthetic pesticides. Paenibacillus popilliae, originally isolated and characterized as causing milky disease in larvae of Japanese beetles (Popillia japonica Newman), has been used in the past as a biocontrol and has potential for development into an efficient biocontrol agent. Using light and electron microscopy to physically define the mechanism involved in the initial stages of milky disease, Splittstoesser and associates showed cellular invasion of larval intestinal epithelial cells by P. popilliae (i.e., host cell attachment, phagocytic engulfment by an epithelial cell, and detainment of the bacterium within the phagocytic vesicle) to be the key mechanism whereby this bacterium crosses the intestinal epithelial lining and causes disease. Unfortunately, the molecular properties surrounding this mechanism in P. popilliae are not known. Knowledge about these pathogenic properties will advance our ability to manipulate this bacterium and help with the development of an effective biological control agent. This knowledge will also have long-term fundamental benefits on the scientific understanding of molecular evolution of enteropathogenic disease mechanisms by extending disease comparison studies into insect pathogenicity. However, before this knowledge can be fully obtained a detailed characterization of the P. popilliae genome is needed. The objective of this investigation is to provide the necessary framework from which to conduct investigations on the mechanism of pathogenicity encoded in P. popilliae. The specific objectives aimed at performing this task are as follows: A) To construct a physical map of the bacterial genome and identify the location of several gene markers on this map. B) To create a Bacterial Artificial Chromosome (BAC) library of the bacterial genome that is coordinated to the physical map of the genome. Several known genes will be isolated from this library as initial studies for isolation of genes associated with pathogenicity. C) To test the insertional mutagenesis capability of Tn916 prior to development of this transposon into an integrative vector for gene identification and isolation.
Project Methods
Construction of a physical map of the P. popilliae genome will be performed using the restriction enzymes I-CeuI, Pme I, and Pac I. Complete and partial digestion of P. popilliae genomic DNA with I-CeuI followed by PFGE separation and measurement and comparison of fragment sizes between complete and partial digests will be used to construct the physical map of I-CeuI restriction sites on the genome of P. popilliae. Complete and partial digestion of genomic DNA with Pme I and Pac I will also be done to determine fragment order and restriction enzyme site locations on the genome. Coordination of these restriction sites with the I-CeuI physical map of restriction sites will involve using purified I-CeuI fragments and digestion with Pme I and Pac I. The physical map of the P. popilliae genome will show the positions of these three enzymes. The P. popilliae genomic map will be further characterization by placement of the genetic markers vanF, cry18Aa, tdk, and the rrn operon ITS regions. Hybridization probes for these markers will be constructed by PCR amplification and after digestion of P. popilliae genomic DNA with Pme I plus Pac I and PFGE, the separated DNA bands will be tested by Southern hybridization analysis to identify restriction fragment(s) on which the gene markers are located. Production of a BAC library for P. popilliae will be performed using the BAC vector, pIndigoBAC536. P. popilliae genomic DNA will be partially digested using HindIII and DNA restriction fragments of approximately 100 Kbp will be obtained using PFGE and extraction of DNA from agarose. Following insertion of these genomic fragments into the BAC vector and electroporation into E. coli, approximately 350 clones will be isolated. The clones will be spot inoculated into 96-well microtiter plates, grown for 3 hrs, and then be frozen at -80C in 25% glycerol. To test the library, Southern hybridization analysis will be performed using colony blots of the 350 clones and hybridization probes for the vanF, cry18Aa, tdk, 16S, 23S, and 5S rRNA genes and for the 3 unique ITS regions. Prior to development of Tn916 into a tool for exploring P. popilliae genomic DNA, the transposon will be tested for suitability as an insertional mutagen. P. popilliae is naturally resistant to vancomycin and disruption of any of the genes responsible for this resistance will render the microbe sensitive to this antibiotic. Tn916-containing P. popilliae strains Tc1001 (resistant to tetracycline; tetr) and Em1001 (resistant to erythromycin; ermr) will be filter-mated and isolates resistant to both tetracycline and erythromycin (i.e., tetr-ermr) will be selected. Both strains are resistant to vancomycin. All tetr-ermr P. popilliae isolates will be tested for sensitivity to vancomycin and sensitive isolates will be screened by PCR amplification of the vanF gene cluster and Southern hybridization analysis for the presence of Tn916 in the vanF gene cluster. Identification of Tn916 in the vanF gene cluster will demonstrate that this transposon is suitable for further development into a molecular tool.

Progress 10/01/03 to 09/30/06

Outputs
Paenibacillus popilliae and Paenibacillus lentimorbus cause milky disease in larvae of several scarab beetle species. P. popilliae is used as a commercial bioinsecticide and to enhance use of this microbe, a better biological understanding is needed. A rough physical map of the P. popilliae genome was produced using the restriction enzymes I-CeuI and Pme I and several gene markers were regionalized onto the map. Enhancement of this map is needed to help assemble a complete P. popilliae genomic sequence. A gene possibly involved with pathogenicity (virB11-like ATPase; Type IV secretory pathway component) was identified. The DNA sequence of plasmid pBP68 has been determined and compared to the sequence of plasmid pBP614. Various sections of DNA sequence present in pBP68 were lacking in pBP614 and coding frame shifts occurred in pBP614. pBP68 and pBP614 exhibited features present in filamentous bacteriophage DNA and it is proposed that a filamentous bacteriophage is the origin of these plasmids. A manuscript reporting these findings is in preparation. This investigation resulted in the development of a DNA fingerprinting protocol for identification of P. popilliae and P. lentimorbus. Although the procedure did not distinguish between the two species, the protocol did produce a unique fingerprint pattern for milky disease bacteria in comparison to other bacteria (i.e., Paenibacillus species). This protocol provides a very easy and fast way to identify and monitor milky disease bacteria. A manuscript describing this protocol and presenting DNA fingerprint patterns for several Paenibacillus species is in production. Comparative analysis of RFLP DNA banding patterns resulting from I-CeuI digested genomic DNA of 53 P. popilliae and P. lentimorbus isolates has shown phylogenic relationships of these two bacteria. P. lentimorbus strains were clearly differentiated from P. popilliae strains. Two groups of P. popilliae and 3 groups of P. lentimorbus were detected. All P. popilliae isolates obtained in Connecticut were found to be limited to one phylogenic group. The Appalachian Mountains represented a geographic separation between the P. popilliae groups. All milky disease bacteria isolated from the commercial insecticide were P. popilliae that belonged to the phylogenetic group found west of the Appalachians. Only one of the P. lentimorbus groups occurred in Connecticut and this group was found only within a limited area. Analysis of the 16S rDNA sequence of these unique P. lentimorbus isolates matched a strain recently identified in Japan (strain Semadara). This phylogenic investigation has helped demonstrate the evolution and differentiation of milky disease bacteria. A manuscript on phylogenic groupings of milky disease bacteria is in preparation. Over the course of this investigation, a total of 40 DNA sequences for P. popilliae and P. lentimorbus have been submitted to the Genbank database. Knowledge on the molecular biological structure and processes of P. popilliae have been gained and are forming the foundation for future molecular investigations on this bacterium.

Impacts
This investigation has increased molecular biological information about the genome of P. popilliae. Use of this information impacts the scientific community by providing a better understanding of this organism. This knowledge is needed to more effectively manipulate this microbe to our advantage. Characterization of the genome will identify genes associated with pathogenicity and will lead to an ability to compare properties to similar microorganisms. Comparative studies will provide an understanding of microbial evolution and development and disease processes. The finding that plasmid DNA in P. popilliae likely originated from filamentous bacteriophage helps research scientists exploring plasmid DNA evolution and provides new ideas into development of tools for genetic engineering of the bacterium. The phylogenic findings of this investigation provide information which will aid future investigations into the problems with efficacy of currently available commercial bioinsecticides using milky disease organisms. Understanding natural strain dispersal will help the development of a insecticide better adapted to a specific locale. Further investigations into the molecular organization are necessary to aid in the development of techniques to manipulate the molecular biochemistry of this bacterium and engineer this microbe to be a more useful commercial bioinsecticide.

Publications

  • No publications reported this period


Progress 01/01/05 to 12/31/05

Outputs
Paenibacillus popilliae is a pathogen of scarab beetle larvae. This microbe is used as a bioinsecticide and a broad molecular understanding of the microbe will help make it a better insecticide. For production of a complete genomic sequence, 13 DNA gene marker fragments isolated from P. popilliae were screened against the genomic scaffolds of Paenibacillus larvae. P. larvae (an insect pathogen causing disease in honey bee larvae) has a published rough genomic sequence consisting of 360 noncontiguous scaffolds. Several P. popilliae genes have been identified in the P. larvae database. Additionally, several genes encoding tRNAs were identified in the P. larvae database. Using this information and the physical map of the P. popilliae genome, a more detailed model of the P. popilliae genome will be constructed. This structure will aid in the assembly of a complete P. popilliae genomic sequence. Genetic engineering of the transposon Tn916 for use in a genetic exchange system and in insertional mutagenesis studies has been performed. A Tn916 construct containing the gene for erythromycin resistance (known to function in P. popilliae) and Tn5 insertion sequences (for random insertion into plasmid vectors) has been inserted into the vector pCMM1. Electroporation of this fusion into Enterococcus faecalis and conjugative transfer from E. faecalis into P. popilliae is to be done for production of insertional mutants. The availability of insertional mutants will help identify genes associated with pathogenicity. A Tn5 derivative containing the erythromycin gene was constructed and inserted into the P. popilliae plasmid pBP68 for work on development of an electroporation protocol for transformation of P. popilliae. pBP68 has been sequenced to completion and determined to have considerable homology to the previously reported sequence of pBP614 (obtained from a New Zealand strain). pBP68 (obtained from a U.S. strain) contained regions of sequence not found in pBP614 that are as yet uncharacterized. Continued work on comparison of plasmid sequences involves sequencing the plasmid pBP94. These results help to compare and contrast the plasmids for function, origin, and evolutionary change based on geographic distribution. The 16S-23S ITS-PCR fingerprinting protocol developed for identification of P. popilliae has been used on other Paenibacillus species and shown to be unique to species. Sequence analysis of 16S rDNA performed on PCR amplified genomic DNA obtained from confirmed Paenibacillus species produced ambiguous results for identification. The 16S-23S ITS-PCR fingerprinting protocol, coupled with 16S rDNA sequence analysis, more accurately identified the bacteria. Results obtained from this investigation provide information on the characterization of the P. popilliae genome. This understanding of the genomic structure provides an ability to effectively manipulate the molecular biochemistry of this bacterium. An ability to engineer DNA within this microbe will provide an ability to probe the disease-causing properties of P. popilliae and help scientists engineer the microbe into a more effective biological insecticide.

Impacts
This investigation into the organization of the P. popilliae genome is providing the necessary information needed by scientists to advance research into other biological properties of this microorganism. An ability to perform comparative analysis between insecticidal microorganisms for understanding microbial evolution and development and an ability to analyze gene content to determine the dispersal of pathogenicity traits in bacteria are part of the knowledge base for scientists to use in future investigations.

Publications

  • No publications reported this period


Progress 01/01/04 to 12/31/04

Outputs
Paenibacillus popilliae has the potential to be a very useful bioinsecticide. Prior to this, knowledge on the molecular biological structure and processes of this organism must be gained. Restriction fragment analysis using I-CeuI plus Pme I and pulsed-field gel electrophoresis (PFGE) has resulted in the construction of a rough physical map for the P. popilliae genome. The map shows a likely location for the chromosomal origin of replication and provides insight into the direction of transcription of the 8 rRNA operons in this microbe. Thirteen DNA marker fragments have been isolated from Paenibacillus popilliae using PCR amplification. These DNA fragments have been cloned, sequenced, and gene identity has been determined by BLAST analysis to the GenBank DNA database. The markers were localized onto I-CeuI and Pme I restriction fragments using Southern hybridization analysis for enhanced characterization of the physical map. These markers included genes for aconitase (citB), phenylalanyl-tRNA synthase (pheT), threonine dehydrogenase (tdh), and vancomycin resistance (van F and van Xf). One marker was found to be a gene encoding for a virB11-like ATPase; a Type IV secretory pathway component. This marker, SEC, is being investigated on the possibility of involvement with pathogenicity. Isolation of randomly generated 150-250 Kb BamHI digested DNA fragments produced from the genomes of P. popilliae, P. lentimorbus, and P. larvae has been performed as a step toward BAC library construction of these microbes. These fragments will be incorporated into the BAC vector pSMART VC, electroporated into Escherichia coli, and transformants selected for production of the BAC libraries. At present, a lambda-phage library of P. popilliae genomic DNA has been revived. This library, consisting of randomized Sau3A digested genomic DNA fragments of approximately 20Kb, is being used to form a separate library of the complete genome, to isolate genes of interest, and to add further characterizing features to the genomic physical map of P. popilliae. Nearly 900 isolated lambda library plaques have been obtained (representing approximately a 5-fold coverage of the genome). A lambda-phage strain was obtained from this library which contains the SEC gene (virB11-like ATPase) and is being characterized further to ascertain whether this gene is associated with pathogenicity. New strains of P. popilliae were isolated from diseased scarab beetle grubs collected from central Missouri. The PCR-based fingerprinting technique using amplification of intertranscribed spacer regions (ITS) in rRNA operons has been used to confirm these isolates as P. popilliae. Comparative analysis of DNA banding patterns resulting from PFGE of I-CeuI digested genomic DNA prepared from these isolates is being performed as part of an investigation to understand the phylogenic organization of P. popilliae. Overall, this investigation continues to improve the characterization of the genome within P. popilliae. The knowledge gained from this investigation will form the foundation from which future molecular investigations to modify and classify this bacterium will be built.

Impacts
Molecular biological studies on the genome of P. popilliae are providing the necessary information needed to advance research on this microorganism. This information is allowing for comparative studies to similar microorganisms and is providing a better understanding of microbial evolution and development. A more complete understanding of insect pathogenic bacteria allows scientists to better modify and utilize these organisms and to better understand the scope of pathogenicity.

Publications

  • Dingman, D. W. 2004. Characterization of Paenibacillus popilliae rRNA operons. Can. J. Microbiol. 50: 779-791.