Lipoproteins Are Potent Activators of Nuclear Factor Kappa B in Mammary Epithelial Cells and Virulence Factors in Mycoplasma bovis Mastitis

Schneider, Peleg; Brill, Re’ella; Schouten, Iftach; Nissim-Eliraz, Einat; Lysnyansky, Inna; Shpigel, Nahum Y.

doi:10.3390/microorganisms10112209

Cited by 4 publications

(4 citation statements)

References 78 publications

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“…Mycoplasma bovis strain PG45 (ATCC 25523 / NCTC 10131) (Hale et al, 1962;Wise et al, 2011) was used in this study and prepared for challenge in lactating mice as previously reported by us (Schneider et al, 2022). Bacteria were propagated at 37 o C in FF modified broth medium (Friis, 1975) supplemented with 0.5% (w/v) sodium pyruvate and 0.005% (w/v) phenol red.…”

Section: Bacterial Strainsmentioning

confidence: 99%

“…Experimental mastitis model systems were established in lactating BALB/c mice using intramammary (IMM) infusion of bacterial suspension to glands L4 and R4 (Figure 1A). We have used E. coli strain P4-NR and the type strain M. bovis PG45 as previously reported by us (Salamon et al, 2020;Schneider et al, 2022). Field strains of Strep.…”

Section: Establishment Of Murine Mastitis Model Systemmentioning

confidence: 99%

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Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

et al. 2023

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Mastitis is one of the most prevalent and economically important diseases of dairy animals. The disease is caused by ascending bacterial infection through the teat canal. Among the most common mastitis-causing bacteria are Gram-negative coliforms, Gram-positive streptococci and staphylococci, and mycoplasma. The most prominent cellular hallmark of acute mammary infection is a massive recruitment of blood neutrophils into the tubular and alveolar milk spaces. The complex biological processes of leukocyte recruitment, activation, adhesion, and migration in the mammary gland remain largely elusive to date. While field research of mastitis in dairy animals contributed a lot to the development of mitigation, control, and even eradication programs, little progress was made toward understanding the molecular mechanisms underlying the pathogenesis of the disease. We report here experimental mastitis model systems in lactating mice challenged with field strains of common udder pathogens in dairy cows. We used these model systems to apply recently developed multiplex gene expression technology (Nanostring nCounter), which enabled us to study the expression of over 700 immune genes. Our analysis revealed a core of 100 genes that are similarly regulated and functionally or physically interacting in E. coli, M. bovis, and Strep uberis murine mastitis. Common significantly enriched gene sets include TNFɑ signaling via NFkB, Interferon gamma and alpha response, and IL6-JAK-STAT3 signaling. In addition, we show a significantly enriched expression of genes associated with neutrophil extracellular traps (NET) in glands challenged by the three pathogens. Ligand-receptor analysis revealed interactions shared by the three pathogens, including the interaction of the cytokines IL1β, IL1ɑ, and TNFɑ with their receptors, and proteins involved in immune cell recruitment such as complement C3 and ICAM1 (with CD11b), chemokines CCL3 and CCL4 (with CCR1), and CSF3 (with CSF3R). Taken together, our results show that mammary infection with E. coli, M. bovis, and Strep uberis culminated in the activation of a conserved core of immune genes and pathways including NET formation.

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Section: Bacterial Strainsmentioning

confidence: 99%

Section: Establishment Of Murine Mastitis Model Systemmentioning

confidence: 99%

Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

et al. 2023

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“…M. bovis mastitis is characterized by massive recruitment of neutrophils into the milk spaces of the mammary gland ( 61 ). Similarly, M. bovis has been shown to stimulate production of neutrophils extracellular traps (NETs) and possess the membrane nuclease, MnuA which degrades the NETs through either exo- or endonuclease activity ( 38 , 62 ).…”

Section: Host Immune Responses Against Mycoplasma Bovis ...mentioning

confidence: 99%

“…M. bovis mastitis is characterized by massive recruitment of neutrophils into the milk spaces of the mammary gland (61).…”

Section: Host Immune Responses Against Mycoplasma Bovis Infection 41 ...mentioning

confidence: 99%

Mycoplasma bovis mastitis in dairy cattle

Gelgie,

Desai,

Gelalcha

et al. 2024

Front. Vet. Sci.

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Mycoplasma bovis has recently been identified increasingly in dairy cows causing huge economic losses to the dairy industry. M. bovis is a causative agent for mastitis, pneumonia, endometritis, endocarditis, arthritis, otitis media, and many other clinical symptoms in cattle. However, some infected cows are asymptomatic or may not shed the pathogen for weeks to years. This characteristic of M. bovis, along with the lack of adequate testing and identification methods in many parts of the world until recently, has allowed the M. bovis to be largely undetected despite its increased prevalence in dairy farms. Due to growing levels of antimicrobial resistance among wild-type M. bovis isolates and lack of cell walls in mycoplasmas that enable them to be intrinsically resistant to beta-lactam antibiotics that are widely used in dairy farms, there is no effective treatment for M. bovis mastitis. Similarly, there is no commercially available effective vaccine for M. bovis mastitis. The major constraint to developing effective intervention tools is limited knowledge of the virulence factors and mechanisms of the pathogenesis of M. bovis mastitis. There is lack of quick and reliable diagnostic methods with high specificity and sensitivity for M. bovis. This review is a summary of the current state of knowledge of the virulence factors, pathogenesis, clinical manifestations, diagnosis, and control of M. bovis mastitis in dairy cows.

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Mycoplasma bovis 5’-nucleotidase is a virulence factor conferring mammary fitness in bovine mastitis

Gelgie,

Schneider,

Citti

et al. 2024

PLoS Pathog

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Nucleases and 5’ nucleotidase (5’-NT) play essential roles in cell biology and are often associated with bacterial virulence. In Mycoplasma spp., which have limited metabolic capacities and rely on nutrient availability, these enzymes are of significant importance for nucleotide salvage. This study explores the potential role of 2 membrane-associated lipoproteins, the major nuclease MnuA and 5’-NT, in Mycoplasma bovis mastitis. Mutants deficient in MnuA (mnuA::Tn) and in 5’-NT (0690::Tn) were identified through genome-wide transposon mutagenesis of M. bovis PG45 type strain and their fitness and virulence were assessed both in vitro, in axenic medium, and in vivo, using murine and cow mastitis models. The mnuA::Tn mutant demonstrated reduced nuclease activity, while 0690::Tn exhibited slow log-phase growth and impaired hydrolase activity towards nucleotides as well as deoxynucleotides (dAMP and dGMP). In comparison to the parent strain, the 0690::Tn mutant displayed markedly reduced fitness, as evidenced by a significant decrease or even absence in post-challenge mycoplasma counts in murine and cow mammary tissues, respectively. Moreover, the 0690::Tn mutant failed to induce mastitis in both experimental models. Conversely, the mnuA::Tn mutant induced inflammation in murine mammary glands, characterized by neutrophil infiltration and increased expression of major inflammatory genes. In cows, the mnuA::Tn was able to cause an increase in somatic cell counts in a manner comparable to the wild type, recruit neutrophils, and induce mastitis. Collectively, these findings provide complementary insights, revealing that disruption of 5’-NT significantly attenuated M. bovis pathogenicity, whereas a MnuA-deficient mutant retained the ability to cause mastitis.

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Lipoproteins Are Potent Activators of Nuclear Factor Kappa B in Mammary Epithelial Cells and Virulence Factors in Mycoplasma bovis Mastitis

Cited by 4 publications

References 78 publications

Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

Mycoplasma bovis mastitis in dairy cattle

Mycoplasma bovis 5’-nucleotidase is a virulence factor conferring mammary fitness in bovine mastitis

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