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A three-way comparative genomic analysis of Mannheimia haemolytica isolates
Paulraj K Lawrence1, Weerayuth Kittichotirat, Jason E McDermott
1Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA. pklawrence@vetmed.wsu.edu
Background:
Mannhemia haemolytica is a Gram-negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen, during stress such as viral infection and transportation to feedlots and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually due to shipping fever. Despite its enormous economic importance there are no specific and accurate genetic markers, which will aid in understanding the pathogenesis and epidemiology of M. haemolytica at molecular level and assist in devising an effective control strategy.
Description:
During our comparative genomic sequence analysis of three Mannheimia haemolytica isolates, we identified a number of genes that are unique to each strain. These genes are "high value targets" for future studies that attempt to correlate the variable gene pool with phenotype. We also identified a number of high confidence single nucleotide polymorphisms (hcSNPs) spread throughout the genome and focused on non-synonymous SNPs in known virulence genes. These SNPs will be used to design new hcSNP arrays to study variation across strains, and will potentially aid in understanding gene regulation and the mode of action of various virulence factors.
Conclusions:
During our analysis we identified previously unknown possible type III secretion effector proteins, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated sequences (Cas). The presence of CRISPR regions is indicative of likely co-evolution with an associated phage. If proven functional, the presence of a type III secretion system in M. haemolytica will help us re-evaluate our approach to study host-pathogen interactions. We also identified various adhesins containing immuno-dominant domains, which may interfere with host-innate immunity and which could potentially serve as effective vaccine candidates.
Insights
Mannheimia haemolytica causes significant cattle losses. Genomic analysis revealed unique genes and high-confidence SNPs, offering new targets for understanding pathogenesis and developing control strategies for this important bovine respiratory disease agent.
Area of Science:
- Bacteriology
- Genomics
- Veterinary Medicine
Background:
- Mannheimia haemolytica is a primary cause of bovine respiratory disease complex, leading to substantial economic losses in the U.S. beef industry.
- This Gram-negative bacterium transitions from commensal to pathogen under stress, causing acute pleuropneumonia (shipping fever).
- Current understanding of M. haemolytica pathogenesis and epidemiology is limited by the absence of specific genetic markers.
Purpose of the Study:
- To identify novel genetic markers for M. haemolytica.
- To explore molecular targets for understanding pathogenesis and developing control strategies.
- To investigate genomic variations within M. haemolytica strains.
Main Methods:
- Comparative genomic sequence analysis of three M. haemolytica isolates.
- Identification of strain-unique genes and high-confidence single nucleotide polymorphisms (hcSNPs).
- Focus on non-synonymous SNPs within known virulence genes for potential array design.
Main Results:
- Discovery of previously unknown type III secretion effector proteins.
- Identification of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) sequences.
- Detection of various adhesins with immuno-dominant domains.
Conclusions:
- The identified unique genes and hcSNPs are valuable targets for future research into M. haemolytica virulence and regulation.
- The potential presence of a type III secretion system necessitates re-evaluation of host-pathogen interaction studies.
- Adhesins with immuno-dominant domains represent promising candidates for vaccine development against M. haemolytica infections.
