Insights into <i>Staphylococcus aureus</i> pathogenesis and genetic diversity in bovine mastitis

Vazquez, Hugo C.; Moliva, Melina; Cerioli, María F.; Vazquez, Martha A.C.; Castañeda, Erika S.; Farías, Emiliano C.; Souza, Miliane M.S.; Reinoso, Elina

doi:10.1590/1678-5150-PVB-7485

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Review Article | Livestock Diseases • Pesq. Vet. Bras. 45 • 2025 • https://doi.org/10.1590/1678-5150-PVB-7485 linkcopy

Insights into Staphylococcus aureus pathogenesis and genetic diversity in bovine mastitis

Insights sobre a patogênese de Staphylococcus aureus e diversidade genética na mastite bovina

Authorship SCIMAGO INSTITUTIONS RANKINGS

Bovine mastitis is the most common infectious disease in dairy herds and causes important economic losses. Various pathogens can cause the disease, with Staphylococcus aureus being one of the most significant. S. aureus can cause clinical, subclinical, and chronic forms of the disease due to a variety of virulence factors, including protein A, coagulase, toxins, and adhesins. The presence of methicillin-resistant S. aureus strains complicates treatment protocols and raises concerns about antimicrobial resistance. The genetic characterization of these strains, utilizing techniques such as molecular typing by pulsed-field gel electrophoresis (PFGE), reveals the existence of different genetic and virulence profiles, as well as the geographical variations in the distribution of these genotypes. The role of next-generation sequencing (NGS) technologies, functional genomics, and multi-omics approaches in the genetic research of bovine mastitis are highlighted, providing a complete understanding of its genetic basis and opening opportunities for targeted interventions and improved disease control strategies in the dairy industry. This review highlights the importance of understanding the genetic diversity and pathogenic mechanisms of S. aureus in bovine mastitis to develop effective disease management strategies and reduce economic losses in the dairy sector globally.

INDEX TERMS:
Infectious disease; dairy herds; genetic characterization; Staphylococcus aureus

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Colégio Brasileiro de Patologia Animal - CBPA Pesquisa Veterinária Brasileira, Caixa Postal 74.591, 23890-000 Rio de Janeiro, RJ, Brasil, Tel./Fax: (55 21) 2682-1081 - Rio de Janeiro - RJ - Brazil
E-mail: pvb@pvb.com.br

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[TFN1] PFGE = pulsed field gel electrophoresis, NGS = next-generation sequencing, MLST = multiple locus sequence typing, RFLP = restriction fragment length polymorphism, MLVA = , MRSA = methicillin-resistant Staphylococcus aureus.

Virulence factor		Description	Associated gene	Function
Immune evasion
	Proteo A	Immune evasion molecule, prevents phagocytosis and complement fixation	spa	Conserved and variable region, extends IgG-binding domain through the cell wall
	Coagulase	Prothrombin activator, protection against phagocytosis	coa	81 bp variable repeat region, strain differentiation
	Capsule	Inhibits phagocytosis, capsule types 5 and 8 are common	-	Protection in animal models, geographical variability
Adhesins
	Clumping factor A (ClfA)	Adhesion to fibrinogen	clfA	Binds to fibrin and fibrinogen
	Intercellular adhesion genes (IcaA, IcaD)	Tissue adhesion	icaA, icaD	Facilitate adhesion to host cells
	Collagen-binding adhesin	Binds to collagen, immune evasion	cna	Adhesion to collagen, immune evasion during human infection
Toxins
	Alpha-toxin (α-toxin)	Cytotoxic toxin, damages host cell membranes	-	Contributes to tissue damage
	Beta-toxin (β-toxin)	Exotoxin involved in mastitis	-	Exacerbates inflammation
	Gamma-toxin (γ-toxin)	Exotoxin involved in mastitis	-	Exacerbates inflammation
	Delta-toxin (δ-toxin)	Exotoxin involved in mastitis	-	Exacerbates inflammation
	Enterotoxins (SEA-SEQ, TSST-1, Eta, Etb)	Heat-stable toxins, cause inflammatory response	-	Potential biohazard, contribute to mastitis
Extracellular regulation
	agr system	Regulator of secretory proteins and virulence factors	agrA, agrB, agrC, agrD, hld	Regulates hemolysins and wall-associated proteins
Biofilm formation
	Polysaccharide intercellular adhesion	Formation of extracellular matrix in biofilm	icaADBC	Biofilm production, antibacterial resistance
	Biofilm-associated protein (Bap)	Biofilm formation, cell communication	bap	Intracellular persistence, antibacterial resistance
	Cytolytic toxins	Involved in biofilm development	-	Facilitate biofilm formation
	agr regulation	Involved in biofilm development	-	Host persistence

Technique	Principle	Advantages	Limitations	Applications
PFGE	Separation of large DNA fragments by pulsed field gel electrophoresis	High discriminatory power, reproducible, and easy to interpret	Labor-intensive, time-consuming, and requires specialized equipment	Establishing clonal relationships, epidemiological investigations
NGS	Sequencing of entire genomes	Provides comprehensive genetic information, high resolution	Expensive, requires bioinformatics expertise	Whole genome analysis, detection of genetic mutations, antibiotic resistance profiling
Multi-omics	Integration of genomics, transcriptomics, proteomics, and metabolomics	Holistic understanding of pathogen biology, identifies functional pathways	Complex data analysis, high cost, and resource-intensive	Understanding pathogen physiology, identifying virulence factors, and developing targeted interventions
spa Typing	PCR amplification of the X region of the spa gene	Fast, cost-effective, good for MRSA typing, geographically adaptable	Lower resolution compared to whole genome sequencing	Rapid typing of MRSA, epidemiological tracking
MLST	Sequencing of multiple housekeeping genes	High reproducibility, good for evolutionary studies	Moderate discriminatory power, more expensive than spa typing	Phylogenetic studies, tracking evolutionary relationships
Plasmid profile analysis	Characterization of plasmid content in strains	Helps in understanding plasmid-mediated antibiotic resistance	Limited to plasmid-carrying strains, lower resolution	Studying horizontal gene transfer, antibiotic resistance mechanisms
RFLP Analysis (MLVA)	Restriction digestion followed by fragment length analysis	Moderate discriminatory power, useful for various loci	Time-consuming, less discriminatory than PFGE or NGS	Typing based on virulence loci , epidemiological studies

Study	Location	Sample size	Typing method	Major findings
Marques et al. (2013)	Fluminense South, Rio Claro, Piraí, Paracambi, Seropédica, Brazil	38 isolates	PFGE	High genetic diversity, no predominant profile, diverse virulence genes
Castañeda Vazquez et al. (2020)	Jalisco, Mexico	32 isolates	PFGE	14.9% genetic variation, 12 PFGE profiles
Dieser et al. (2017)	Argentina	43 isolates	PFGE	2 PFGE profiles (A and B), high virulence diversity
Vaughn et al. (2020)	Tennessee, USA	111 isolates	PFGE	16 PFGE types, no association with virulence factors
Hoekstra et al. (2020)	11 countries	125 isolates from CM 151 from SCM	Clonal Complex Analysis	CC479 associated with clinical mastitis
Monistero et al. (2018)	8 countries	120 isolates	RS-PCR	Country-specific genotypes, wide genetic diversity
Leijon et al. (2021)	Sweden	225 and 229 isolates collected 2002-2003, 2013- 2018	cgMLST	Clonal complexes CC97, CC133, CC151 prevalent over time