Episomal virulence gene burden in coliform mastitis pathogens is linked to TLR4/CD-14/LRRK1 driven oxidative inflammatory signaling and systemic immunometabolic disturbances in Holstein dairy cows.
Source: PubMed, NCBI / U.S. National Library of Medicine
Acute coliform mastitis (ACM) is an inflammatory disease of the mammary gland and may be accompanied by fatal systemic manifestations. The impact of virulence factors of coliform pathotypes on ACM severity remains unclear. The current work investigated the molecular events by which pathogens' virulence broadens local mammary infection to metabolic disturbances and systemic outcomes. A total of 168 Holstein cows with ACM were investigated; 18 met the inclusion criteria and were categorized into localized ACM (LACM, n = 9) and systemic ACM (SACM, n = 9) based on udder inflammation severity, clinical manifestations, and SCC, along with 10 healthy controls. Coliform bacteria (Escherichia coli and Klebsiella pneumoniae) were identified by MALDI-TOF MS, serotyped by O/H/K agglutination, screened for antimicrobial susceptibility, and virulence determinants by PCR. Tested SACM strains exhibited XDR phenotypes with high MAR indices. They harbored multiple virulence determinants (iss, ompT, iucD), whereas LACM strains carried only iss and were associated with localized inflammatory reactions. Antimicrobial peptides, acute-phase proteins, markers of hepatobiliary/renal and cardiac injury, metabolic imbalance, and TLR4/CD-14/LRRK-1-mediated inflammatory signaling and suppression of antioxidant defense were more intensified in SACM than in LACM and controls. The correlation matrix and Mantel test revealed significant integration of virulence-induced systemic host responses in the SACM gro
Abstract
Acute coliform mastitis (ACM) is an inflammatory disease of the mammary gland and may be accompanied by fatal systemic manifestations. The impact of virulence factors of coliform pathotypes on ACM severity remains unclear. The current work investigated the molecular events by which pathogens' virulence broadens local mammary infection to metabolic disturbances and systemic outcomes. A total of 168 Holstein cows with ACM were investigated; 18 met the inclusion criteria and were categorized into localized ACM (LACM, n = 9) and systemic ACM (SACM, n = 9) based on udder inflammation severity, clinical manifestations, and SCC, along with 10 healthy controls. Coliform bacteria (Escherichia coli and Klebsiella pneumoniae) were identified by MALDI-TOF MS, serotyped by O/H/K agglutination, screened for antimicrobial susceptibility, and virulence determinants by PCR. Tested SACM strains exhibited XDR phenotypes with high MAR indices. They harbored multiple virulence determinants (iss, ompT, iucD), whereas LACM strains carried only iss and were associated with localized inflammatory reactions. Antimicrobial peptides, acute-phase proteins, markers of hepatobiliary/renal and cardiac injury, metabolic imbalance, and TLR4/CD-14/LRRK-1-mediated inflammatory signaling and suppression of antioxidant defense were more intensified in SACM than in LACM and controls. The correlation matrix and Mantel test revealed significant integration of virulence-induced systemic host responses in the SACM group, evidenced by strong inter-organ biomarker associations and coordinated oxidative-inflammatory cascade networks (r>0.75, P≤ 0.01). Composite host response modeling supported that virulence traits are linked to mastitis severity. Thus, combining virulence profiling with host-response biomarkers offers an approach to forecasting mastitis progression toward systemic oxidative metabolic dysregulation and to improving clinical management.