Bovine mastitis is an inflammation of the mammary gland, which could be the result of allergy, physical trauma, or invasion by pathogens as Streptococcus uberis. This pathogen is an environmental pathogen associated with subclinical and clinical intramammary infection (IMI) in both lactating and non-lactating cows, which can persist in the udder and cause a chronic infection in the mammary gland. In spite of the important economic losses and increased prevalence caused by S. uberis mastitis, virulence factors involved in bacterial colonization of mammary glands and the pathogenic mechanisms are not yet clear. In the last 30 years, several studies have defined adherence and internalization of S. uberis as the early stages in IMI. S. uberis adheres to and invades into mammary gland cells, and this ability has been observed in in vitro assays. Until now, these abilities have not been determined in vivo challenges since they have been difficult to study. Bacterial surface proteins are able to bind to extracellular matrix protein components such as fibronectin, collagen and laminin, as well as proteins in milk. These proteins play a role in adhesion to host cells and have been denominated microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). This article aims to summarize our current knowledge on the most relevant properties of the potential factors involved in the early pathogenesis of S. uberis mastitis.

Consejo Nacional de Investigaciones Científicas y Técnicas Buenos Aires Argentina

Departamento de Microbiología e Inmunología Facultad de Ciencias Exactas Físico Químicas y Naturales Universidad Nacional de Río Cuarto Ruta Nacional 36 Km 601 X5804ZAB Río Cuarto Córdoba Argentina

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Abureema S, Deighton MA, Mantri N (2019) A novel subtraction diversity array distinguishes between clinical and non-clinical Streptococcus uberis and identifies potential virulence determinants. Vet Microbiol 237:108385. https://doi.org/10.1016/j.vetmic.2019.108385 PubMed DOI

Abureema S, Smooker P, Malmo J, Deighton MA (2014) Molecular epidemiology of recurrent clinical mastitis due to Streptococcus uberis: evidence of both an environmental source and recurring infection with the same strain. J Dairy Sci 97:285–290. https://doi.org/10.3168/jds.2013-7074 PubMed DOI

Addis MF, Tanca A, Uzzau S et al (2016) The bovine milk microbiota: insights and perspectives from-omics studies. Mol Biosyst 2(8):2359–2372. https://doi.org/10.1039/c6mb00217j DOI

Ajello M, Greco R, Giansanti F et al (2002) Anti-invasive activity of bovine lactoferrin towards group a streptococci. Biochemistry and Cell Biology. NRC Research Press Ottawa, Canada, pp 119–124

Almeida RA, Dunlap JR, Oliver SP (2010) Binding of host factors influences internalization and intracellular trafficking of Streptococcus uberis in bovine mammary epithelial cells. Vet Med Int 2010:1–8. https://doi.org/10.4061/2010/319192 DOI

Almeida RA, Dego OK, Prado ME et al (2015a) Protective effect of anti-SUAM antibodies on Streptococcus uberis mastitis. Vet Res 46:1–6. https://doi.org/10.1186/s13567-015-0271-3 DOI

Almeida RA, Dego OK, Headrick SI et al (2015b) Role of Streptococcus uberis adhesion molecule in the pathogenesis of Streptococcus uberis mastitis. Vet Microbiol 179:332–335. https://doi.org/10.1016/j.vetmic.2015.07.005 PubMed DOI

Almeida RA, Luther DA, Douglas VL et al (2006a) Identification, isolation, and partial characterization of a novel Streptococcus uberis adhesion molecule (SUAM). Vet Microbiol 115:183–191. https://doi.org/10.1016/j.vetmic.2006.02.005 PubMed DOI

Almeida RA, Luther DA, Kumar SJ et al (1996) Adherence of Streptococcus uberis to bovine mammary epithelial cells and to extracellular matrix proteins. J Vet Med Ser B 43:385–392. https://doi.org/10.1111/j.1439-0450.1996.tb00330.x DOI

Almeida RA, Luther DA, Nair R, Oliver SP (2003) Binding of host glycosaminoglycans and milk proteins: Possible role in the pathogenesis of Streptococcus uberis mastitis. Vet Microbiol 94:131–141. https://doi.org/10.1016/S0378-1135(03)00078-6 PubMed DOI

Almeida RA, Luther DA, Oliver SP (2006b) Pathogenic strategies of mastitis pathogens

Almeida RA, Luther DA, Oliver SP (1999) Incubation of Streptococcus uberis with extracellular matrix proteins enhances adherence to and internalization into bovine mammary epithelial cells. FEMS Microbiol Lett 178:81–85. https://doi.org/10.1016/S0378-1097(99)00336-5 PubMed DOI

Almeida RA, Luther DA, Patel D, Oliver SP (2011) Predicted antigenic regions of Streptococcus uberis adhesion molecule (SUAM) are involved in adherence to and internalization into mammary epithelial cells. Vet Microbiol 148:323–328. https://doi.org/10.1016/j.vetmic.2010.09.017

Almeida RA, Oliver SP (1993) Antiphagocytic effect of the capsule of Streptococcus uberis. J Vet Med Ser B 40:707–714. https://doi.org/10.1111/j.1439-0450.1993.tb00195.x DOI

Almeida RA, Oliver SP (2001) Role of collagen in adherence of Streptococcus uberis to bovine mammary epithelial cells. J Vet Med Ser B 48:759–763. https://doi.org/10.1046/j.1439-0450.2001.00506.x DOI

Almeida RA, Oliver SP (2006) Trafficking of Streptococcus uberis in bovine mammary epithelial cells. Microb Pathog 41:80–89. https://doi.org/10.1016/j.micpath.2006.04.007 PubMed DOI

Andreini C, Banci L, Bertini I, Rosato A (2006) Counting the zinc-proteins encoded in the human genome. J Proteome Res 5:196–201. https://doi.org/10.1021/pr050361j PubMed DOI

Andreini C, Bertini I (2012) A bioinformatics view of zinc enzymes. J Inorg Biochem 111:150–156. https://doi.org/10.1016/j.jinorgbio.2011.11.020 PubMed DOI

Andreini C, Bertini I, Cavallaro G et al (2008) Metal ions in biological catalysis: from enzyme databases to general principles. J Biol Inorg Chem 13:1205–1218. https://doi.org/10.1007/s00775-008-0404-5 PubMed DOI

Aranda J, Garrido ME, Fittipaldi N et al (2009) Protective capacities of cell surface-associated proteins of Streptococcus suis mutants deficient in divalent cation-uptake regulators. Microbiology 155:1580–1587. https://doi.org/10.1099/mic.0.026278-0 PubMed DOI

Ashraf A, Imran M (2018) Diagnosis of bovine mastitis: from laboratory to farm. Trop Anim Health Prod 50:1193–1202. https://doi.org/10.1007/s11250-018-1629-0 PubMed DOI

Babbar A, Itzek A, Pieper DH, Nitsche-Schmitz DP (2018) Detection of Streptococcus pyogenes virulence genes in Streptococcus dysgalactiae subsp. equisimilis from Vellore. India Folia Microbiol (praha) 63:581–586. https://doi.org/10.1007/s12223-018-0595-2 DOI

Ballas P, Gabler C, Wagener K et al (2020) Streptococcus uberis strains originating from bovine uteri provoke upregulation of pro-inflammatory factors mRNA expression of endometrial epithelial cells in vitro. Vet Microbiol 245:108710. https://doi.org/10.1016/j.vetmic.2020.108710 PubMed DOI

Barnett TC, Scott JR (2002) Differential recognition of surface proteins in Streptococcus pyogenes by two sortase gene homologs. J Bacteriol 184:2181–2191. https://doi.org/10.1128/JB.184.8.2181-2191.2002 PubMed DOI PMC

Bayle L, Chimalapati S, Schoehn G et al (2011) Zinc uptake by Streptococcus pneumoniae depends on both AdcA and AdcAII and is essential for normal bacterial morphology and virulence. Mol Microbiol 82:904–916. https://doi.org/10.1111/j.1365-2958.2011.07862.x PubMed DOI

Beckmann C, Waggoner JD, Harris TO et al (2002) Identification of novel adhesins from group B streptococci by use of phage display reveals that C5a peptidase mediates fibronectin binding. Infect Immun 70:2869–2876. https://doi.org/10.1128/IAI.70.6.2869-2876.2002 PubMed DOI PMC

Bogni CI, Odierno LM, Raspanti CG et al (2011) War against mastitis: current concepts on controlling bovine mastitis pathogens

Boonyayatra S, Tharavichitkul P, Oliver SPSP (2018) Virulence-associated genes and molecular typing of Streptococcus uberis associated with bovine mastitis in northern Thailand. Turkish J Vet Anim Sci 42:73–81. https://doi.org/10.3906/vet-1704-75 DOI

Bradley AJ (2002) Bovine mastitis: an evolving disease. Vet J 164:116–128. https://doi.org/10.1053/tvjl.2002.0724 PubMed DOI

Bradley AJ, Leach KA, Breen JE et al (2007) Survey of the incidence and aetiology of mastitis on diary farms in England and Wales. Vet Rec 160:253–258. https://doi.org/10.1136/vr.160.8.253 PubMed DOI

Braymer JJ, Giedroc DP (2014) Recent developments in copper and zinc homeostasis in bacterial pathogens. Curr Opin Chem Biol 19:59–66 DOI

Brown LR, Gunnell SM, Cassella AN et al (2016) AdcAII of Streptococcus pneumoniae affects pneumococcal invasiveness. PLoS ONE 11:e0146785. https://doi.org/10.1371/journal.pone.0146785 PubMed DOI PMC

Calonzi D, Romano A, Monistero V et al (2020) Technical note: development of multiplex PCR assays for the molecular characterization of Streptococcus uberis strains isolated from bovine mastitis. J Dairy Sci 103:915–921. https://doi.org/10.3168/jds.2019-16823 PubMed DOI

Cerasi M, Ammendola S, Battistoni A (2013) Competition for zinc binding in the host-pathogen interaction. Front Cell Infect Microbiol 3:108 DOI

Chaneton L, Tirante L, Maito J et al (2008) Relationship between milk lactoferrin and etiological agent in the mastitic bovine mammary gland. J Dairy Sci 91:1865–1873. https://doi.org/10.3168/jds.2007-0732 PubMed DOI

Chen X, Kerro Dego O, Almeida RA et al (2011) Deletion of sua gene reduces the ability of Streptococcus uberis to adhere to and internalize into bovine mammary epithelial cells. Vet Microbiol 147:426–434. https://doi.org/10.1016/j.vetmic.2010.07.006 PubMed DOI

Cheng Q, Stafslien D, Purushothaman S, Cleary PP (2002) The group B streptococcal C5a peptidase is both a specific protease and an invasin. Infect Immun 70:2408–2413. https://doi.org/10.1128/IAI.70.5.2408-2413.2002 PubMed DOI PMC

Christie J, McNab R, Jenkinson HF (2002) Expression of fibronectin-binding protein FbpA modulates adhesion in Streptococcus gordonii. Microbiology 148:1615–1625. https://doi.org/10.1099/00221287-148-6-1615 PubMed DOI

Cleary PP, Peterson J, Chen CC, Nelson C (1991) Virulent human strains of group G streptococci express a C5a peptidase enzyme similar to that produced by group A streptococci. Infect Immun 59

Cleary PP, Prahbu U, Dale JB et al (1992) Streptococcal C5a peptidase is a highly specific endopeptidase. Infect Immun 60:5219–5223. https://doi.org/10.1128/iai.60.12.5219-5223.1992 PubMed DOI PMC

Collado R, Montbrau C, Sitjà M, Prenafeta A (2018) Study of the efficacy of a Streptococcus uberis mastitis vaccine against an experimental intramammary infection with a heterologous strain in dairy cows. J Dairy Sci 101:10290–10302. https://doi.org/10.3168/jds.2018-14840 PubMed DOI

Collado R, Prenafeta A, González-González L et al (2016) Probing vaccine antigens against bovine mastitis caused by Streptococcus uberis. Vaccine 34:3848–3854. https://doi.org/10.1016/j.vaccine.2016.05.044 PubMed DOI

Courtney HS, Li Y, Dale JB, Hasty DL (1994) Cloning, sequencing, and expression of a fibronectin/fibrinogen-binding protein from group A streptococci. Infect Immun 62:3937–3946. https://doi.org/10.1128/iai.62.9.3937-3946.1994 PubMed DOI PMC

Crowley RC, Leigh JA, Ward PN et al (2011) Differential protein expression in Streptococcus uberis under planktonic and biofilm growth conditions. Appl Environ Microbiol 77:382–384. https://doi.org/10.1128/aem.01099-10 PubMed DOI

Cunningham MW (2000) Pathogenesis of group a streptococcal infections. Clin Microbiol Rev 13:470–511 DOI

Davies PL, Leigh JA, Bradley AJ et al (2016) Molecular epidemiology of Streptococcus uberis clinical mastitis in dairy herds: strain heterogeneity and transmission. J Clin Microbiol 54:68–74. https://doi.org/10.1128/JCM.01583-15 PubMed DOI

Decaria L, Bertini I, Williams JP (2010) Zinc proteomes, phylogenetics and evolution. Metallomics 2:706–709. https://doi.org/10.1039/c0mt00024h PubMed DOI

Dego OK, Almeida RA, Saxton AM et al (2018) Bovine intramammary infection associated immunogenic surface proteins of Streptococcus uberis. Microb Pathog 115:304–311. https://doi.org/10.1016/j.micpath.2017.12.046 PubMed DOI

Diacovich L, Gorvel JP (2010) Bacterial manipulation of innate immunity to promote infection. Nat Rev Microbiol 8:117–128 DOI

Dintilhac A, Alloing G, Granadel C, Claverys JP (1997) Competence and virulence of Streptococcus pneumoniae : Adc and PsaA mutants exhibit a requirement for Zn and Mn resulting from inactivation of putative ABC metal permeases. Mol Microbiol 25:727–739. https://doi.org/10.1046/j.1365-2958.1997.5111879.x PubMed DOI

Dintilhac A, Claverys JP (1997) The adc locus, which affects competence for genetic transformation in Streptococcus pneumoniae, encodes an ABC transporter with a putative lipoprotein homologous to a family of streptococcal adhesins. Res Microbiol 148:119–131. https://doi.org/10.1016/S0923-2508(97)87643-7 PubMed DOI

Egan SA, Kurian D, Ward PN et al (2010) Identification of sortase A (SrtA) substrates in Streptococcus uberis: evidence for an additional hexapeptide (LPXXXD) sorting motif. J Proteome Res 9:1088–1095. https://doi.org/10.1021/pr901025w PubMed DOI

Egan SA, Ward PN, Watson M et al (2012) Vru (Sub0144) controls expression of proven and putative virulence determinants and alters the ability of Streptococcus uberis to cause disease in dairy cattle. Microbiol (united Kingdom) 158:1581–1592. https://doi.org/10.1099/mic.0.055863-0 DOI

Elsner A, Kreikemeyer B, Braun-Kiewnick A et al (2002) Involvement of Lsp, a member of the LraI-lipoprotein family in Streptococcus pyogenes, in eukaryotic cell adhesion and internalization. Infect Immun 70:4859–4869. https://doi.org/10.1128/IAI.70.9.4859-4869.2002 PubMed DOI PMC

Fang W, Almeida RA, Oliver SP (2000) Effects of lactoferrin and milk on adherence of Streptococcus uberis to bovine mammary epithelial cells. Am J Vet Res 61:275–279. https://doi.org/10.2460/ajvr.2000.61.275 PubMed DOI

Fang W, Oliver SP (1999) Identification of lactoferrin-binding proteins in bovine mastitis-causing Streptococcus uberis. FEMS Microbiol Lett 176:91–96. https://doi.org/10.1016/S0378-1097(99)00224-4 PubMed DOI

Fessia AS, Dieser SA, Raspanti CG, Odierno LM (2019) Genotyping and study of adherence-related genes of Streptococcus uberis isolates from bovine mastitis. Microb Pathog 130:295–301. https://doi.org/10.1016/j.micpath.2019.03.027 PubMed DOI

Fessia AS, Dieser SA, Renna MS et al (2020) Relative expression of genes associated with adhesion to bovine mammary epithelial cells by Streptococcus uberis. Res Vet Sci 132:33–41. https://doi.org/10.1016/j.rvsc.2020.05.016 PubMed DOI

Finlay BB, Cossart P (1997) Exploitation of mammalian host cell functions by bacterial pathogens. Science (80-) 276:718–725. https://doi.org/10.1126/science.276.5313.718

Gilbert FB, Luther DA, Oliver SP (1997) Induction of surface-associated proteins of Streptococcus uberis by cultivation with extracellular matrix components and bovine mammary epithelial cells. FEMS Microbiol Lett 156:161–164. https://doi.org/10.1111/j.1574-6968.1997.tb12722.x

Gutekunst H, Eikmanns BJ, Reinscheid DJ (2004) The novel fibrinogen-binding protein FbsB promotes Streptococcus agalactiae invasion into epithelial cells. Infect Immun 72:3495–3504. https://doi.org/10.1128/IAI.72.6.3495-3504.2004 PubMed DOI PMC

Hagiwara SI, Kawai K, Anri A, Nagahata H (2003) Lactoferrin concentrations in milk from normal and subclinical mastitic cows. J Vet Med Sci 65:319–323. https://doi.org/10.1292/jvms.65.319 PubMed DOI

Hamada S, Kawabata S, Nakagawa I (2015) Molecular and genomic characterization of pathogenic traits of group a Streptococcus pyogenes. Proc. Japan Acad. Ser B Phys Biol Sci 91:539–559

Harmon RJ, Schanbacher FL, Ferguson LC, Smith KL (1975) Concentration of lactoferrin in milk of normal lactating cows and changes occurring during mastitis. Am J Vet Res 36:1001–1007 PubMed

Heikkilä AM, Liski E, Pyörälä S, Taponen S (2018) Pathogen-specific production losses in bovine mastitis. J Dairy Sci 101:9493–9504. https://doi.org/10.3168/jds.2018-14824 PubMed DOI

Henderson B, Nair S, Pallas J, Williams MA (2011) Fibronectin: a multidomain host adhesin targeted by bacterial fibronectin-binding proteins. FEMS Microbiol Rev 35:147–200. https://doi.org/10.1111/j.1574-6976.2010.00243.x PubMed DOI

Hogan J, Smith KL (2012) Managing environmental mastitis. Vet. Clin North Am - Food Anim Pract 28:217–224 DOI

Honsa ES, Johnson MD, Rosch JW (2013) The roles of transition metals in the physiology and pathogenesis of Streptococcus pneumoniae. Front Cell Infect Microbiol 3:92

Hoque MN, Istiaq A, Rahman MS et al (2020) Microbiome dynamics and genomic determinants of bovine mastitis. Genomics 112(6):5188–5203. https://doi.org/10.1016/j.ygeno.2020.09.039 PubMed DOI

Hossain M, Egan SA, Coffey TJ et al (2015) Virulence related sequences; insights provided by comparative genomics of Streptococcus uberis of differing virulence. BMC Genomics 16:1–13. https://doi.org/10.1186/s12864-015-1512-6 DOI

Hurley WL, Rejman JJ (1993) Bovine lactoferrin in involuting mammary tissue. Cell Biol Int 17:283–290. https://doi.org/10.1006/cbir.1993.1064 PubMed DOI

Jaffe J, Natanson-Yaron S, Caparon MG, Hanski E (1996) Protein F2, a novel fibronectin-binding protein from Streptococcus pyogenes, possesses two binding domains. Mol Microbiol 21:373–384. https://doi.org/10.1046/j.1365-2958.1996.6331356.x PubMed DOI

Jiang M, Babiuk LA, Potter AA (1996) Cloning, sequencing and expression of the CAMP factor gene of Streptococcus uberis. Microb Pathog 20:297–307. https://doi.org/10.1006/mpat.1996.0028 PubMed DOI

Joh D, Wann ER, Kreikemeyer B et al (1999) Role of fibronectin-binding MSCRAMMs in bacterial adherence and entry into mammalian cells. Matrix Biol 18:211–223. https://doi.org/10.1016/S0945-053X(99)00025-6 PubMed DOI

Kaczorek E, Małaczewska J, Wójcik R, Siwicki AK (2017) Biofilm production and other virulence factors in Streptococcus spp. isolated from clinical cases of bovine mastitis in Poland. BMC Vet Res 13:1–7. https://doi.org/10.1186/s12917-017-1322-y DOI

Kawai K, Hagiwara S, Anri A, Nagahata H (1999) Lactoferrin concentration in milk of bovine clinical mastitis. Vet Res Commun 23:391–398. https://doi.org/10.1023/A:1006347423426 PubMed DOI

Keane OM (2019) Symposium review: intramammary infections—major pathogens and strain-associated complexity. J Dairy Sci 102:4713–4726. https://doi.org/10.3168/jds.2018-15326 PubMed DOI

Keane OM, Budd KE, Flynn J, McCoy F (2013) Pathogen profile of clinical mastitis in Irish milk-recording herds reveals a complex aetiology. Vet Rec 173:17. https://doi.org/10.1136/vr.101308 PubMed DOI

Kerro-Dego O, Prado ME, Chen X, Luther DA, Almeida RA, Oliver SP (2011) PGh9:ISS1 transpositional mutations in Streptococcus uberis UT888 causes reduced bacterial adherence to and internalization into bovine mammary epithelial cells. Vet Microbiol 151:379–385. https://doi.org/10.1016/j.vetmic.2011.04.001

Klaas IC, Zadoks RN (2018) An update on environmental mastitis: challenging perceptions. Transbound Emerg Dis 65:166–185. https://doi.org/10.1111/tbed.12704 PubMed DOI

Komine KI, Komine Y, Kuroishi T et al (2005) Small molecule lactoferrin with an inflammatory effect but no apparent antibacterial activity in mastitic mammary gland secretion. J Vet Med Sci 67:667–677. https://doi.org/10.1292/jvms.67.667 PubMed DOI

Kromker V (2014) Bovine Streptococcus uberis intramammary infections and mastitis Clin Microbiol Open Access 03 https://doi.org/10.4172/2327-5073.1000157

Lasagno MC, Reinoso EB, Dieser SA et al (2011) Phenotypic and genotypic characterization of Streptococcus uberis isolated from bovine subclinical mastitis in Argentinean dairy farms. Rev Argent Microbiol 43:212–217. https://doi.org/10.1590/S0325-75412011000300009 PubMed DOI

LeBlanc SJ, Lissemore KD, Kelton DF et al (2006) Major advances in disease prevention in dairy cattle. J Dairy Sci 89:1267–1279. https://doi.org/10.3168/jds.S0022-0302(06)72195-6 PubMed DOI

Leelahapongsathon K, Schukken YH, Srithanasuwan A, Suriyasathaporn W (2020) Molecular epidemiology of Streptococcus uberis intramammary infections: persistent and transient patterns of infection in a dairy herd. J Dairy Sci 103:3565–3576. https://doi.org/10.3168/jds.2019-17281 PubMed DOI

Leigh JA (1999) Streptococcus uberis: a permanent barrier to the control of bovine mastitis? Vet J 157:225–238. https://doi.org/10.1053/tvjl.1998.0298 PubMed DOI

Leigh JA, Egan SA, Ward PN et al (2010) Sortase anchored proteins of Streptococcus uberis play major roles in the pathogenesis of bovine mastitis in dairy cattle. Vet Res 41 https://doi.org/10.1051/vetres/2010036

Lewis VG, Ween MP, McDevitt CA (2012) The role of ATP-binding cassette transporters in bacterial pathogenicity. Protoplasma 249(4):919–942

Li Q, Liu H, Du D et al (2015) Identification of novel laminin-and fibronectin-binding proteins by Far-Western Blot: capturing the adhesins of Streptococcus suis Type 2. Front Cell Infect Microbiol 5:1–11. https://doi.org/10.3389/fcimb.2015.00082 DOI

Linke C, Caradoc-Davies TT, Young PG et al (2009) The laminin-binding protein Lbp from Streptococcus pyogenes is a zinc receptor. J Bacteriol 191:5814–5823. https://doi.org/10.1128/JB.00485-09 PubMed DOI PMC

Lo HH, Cheng WS (2015) Distribution of virulence factors and association with emm polymorphism or isolation site among beta-hemolytic group G Streptococcus dysgalactiae subspecies equisimilis. APMIS 123:45–52. https://doi.org/10.1111/apm.12305 PubMed DOI

Loisel E, Jacquamet L, Serre L et al (2008) AdcAII, anew pneumococcal Zn-binding protein homologous with ABC transporters: biochemical and structural analysis. J Mol Biol 381:594–606. https://doi.org/10.1016/j.jmb.2008.05.068 PubMed DOI

Lopez-Benavides MG, Williamson JH, Pullinger GD et al (2007) Field observations on the variation of Streptococcus uberis populations in a pasture-based dairy farm. J Dairy Sci 90:5558–5566. https://doi.org/10.3168/jds.2007-0194 PubMed DOI

Luther DA, Almeida RA, Oliver SP (2008) Elucidation of the DNA sequence of Streptococcus uberis adhesion molecule gene (sua) and detection of sua in strains of Streptococcus uberis isolated from geographically diverse locations. Vet Microbiol 128:304–312. https://doi.org/10.1016/j.vetmic.2007.10.015 PubMed DOI

Makthal N, Nguyen K, Do H et al (2017) A critical role of zinc importer AdcABC in group A Streptococcus-host interactions during infection and its implications for vaccine development. EBioMedicine 21:131–141. https://doi.org/10.1016/j.ebiom.2017.05.030 PubMed DOI PMC

Matthews R, Almeida RA, Oliver SP (1994) Bovine mammary epithelial cell invasion by Streptococcus uberis. Infect Immun 62:5641–5646. https://doi.org/10.1128/iai.62.12.5641-5646.1994 PubMed DOI PMC

Mitrakul K, Loo CY, Gyurko C et al (2005) Mutational analysis of the adcCBA genes in Streptococcus gordonii biofilm formation. Oral Microbiol Immunol 20:122–127. https://doi.org/10.1111/j.1399-302X.2004.00205.x PubMed DOI

Moshynskyy I, Jiang M, Fontaine MC et al (2003) Characterization of a bovine lactoferrin binding protein of Streptococcus uberis. Microb Pathog 35:203–215. https://doi.org/10.1016/S0882-4010(03)00150-5 PubMed DOI

Moulin P, Patron K, Cano C et al (2016) The Adc/Lmb system mediates zinc acquisition in Streptococcus agalactiae and contributes to bacterial growth and survival. J Bacteriol 198:3265–3277. https://doi.org/10.1128/JB.00614-16 PubMed DOI PMC

NMC (2009) Recommended mastitis control program. Madison,WI

Nobbs AH, Lamont RJ, Jenkinson HF (2009) Streptococcus adherence and colonization. Microbiol Mol Biol Rev 73:407–450. https://doi.org/10.1128/mmbr.00014-09 PubMed DOI PMC

Oliver SP, Almeida RA, Calvinho LF (1998) Virulence factors of Streptococcus uberis isolated from cows with mastitis. J Vet Med Ser B 45:461–471. https://doi.org/10.1111/j.1439-0450.1998.tb00817.x DOI

Pancholi V, Fischetti VA (1993) Glyceraldehyde-3-phosphate dehydrogenase on the surface of group A streptococci is also an ADP-ribosylating enzyme. Proc Natl Acad Sci U S A 90:8154–8158. https://doi.org/10.1073/pnas.90.17.8154 PubMed DOI PMC

Panina EM, Mironov AA, Gelfand MS (2003) Comparative genomics of bacterial zinc regulons: enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins. Proc Natl Acad Sci U S A 100:9912–9917. https://doi.org/10.1073/pnas.1733691100 PubMed DOI PMC

Parin U, Krkan S, Cicek E, Yüksel HT (2017) Detection of virulence genes in Streptococcus uberis isolated from bovine mastitis in Aydn province by multiplex polymerase chain reaction. Saglk Bilim Tip Dergisi, Frat Üniversitesi 31:213–219

Patel D, Almeida RA, Dunlap JR, Oliver SP (2009) Bovine lactoferrin serves as a molecular bridge for internalization of Streptococcus uberis into bovine mammary epithelial cells. Vet Microbiol 137:297–301. https://doi.org/10.1016/j.vetmic.2009.01.013 PubMed DOI

Patti JM, Allen BL, McGavin MJ, Hook M (1994) MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol 48:585–617. https://doi.org/10.1146/annurev.mi.48.100194.003101 PubMed DOI

Pedersen LH, Aalbæk B, Røntved CM et al (2003) Early pathogenesis and inflammatory response in experimental bovine mastitis due to Streptococcus uberis. J Comp Pathol 128:156–164. https://doi.org/10.1053/jcpa.2002.0620 PubMed DOI

Perrig MS, Ambroggio MB, Buzzola FR et al (2015) Genotyping and study of the pauA and sua genes of Streptococcus uberis isolates from bovine mastitis. Rev Argent Microbiol 47:282–294. https://doi.org/10.1016/j.ram.2015.06.007 PubMed DOI

Perrig MS, Veaute C, Renna MS et al (2017) Assessment of the potential utility of different regions of Streptococcus uberis adhesion molecule (SUAM) for mastitis subunit vaccine development. Microb Pathog 105:273–279. https://doi.org/10.1016/j.micpath.2017.02.035 PubMed DOI

Phuektes P, Mansell PD, Dyson RS et al (2001) Molecular epidemiology of Streptococcus uberis isolates from dairy cows with mastitis. J Clin Microbiol 39:1460–1466. https://doi.org/10.1128/JCM.39.4.1460-1466.2001 PubMed DOI PMC

Plumptre CD, Eijkelkamp BA, Morey JR et al (2014) AdcA and AdcAII employ distinct zinc acquisition mechanisms and contribute additively to zinc homeostasis in Streptococcus pneumoniae. Mol Microbiol 91:834–851. https://doi.org/10.1111/mmi.12504 PubMed DOI

Prado ME, Almeida RA, Ozen C et al (2011) Vaccination of dairy cows with recombinant Streptococcus uberis adhesion molecule induces antibodies that reduce adherence to and internalization of S. uberis into bovine mammary epithelial cells. Vet Immunol Immunopathol 141:201–208. https://doi.org/10.1016/j.vetimm.2011.02.023 PubMed DOI

Pryor SM (2008) Bovine mastitis and ecology of Streptococcus uberis. 1994

Rabot A, Wellnitz O, Meyer HD, Bruckmaier RM (2007) Use and relevance of a bovine mammary gland explant model to study infection responses in bovine mammary tissue. J Dairy Res 74:93–99. https://doi.org/10.1017/S0022029906002147 PubMed DOI

Ragunathan P, Sridaran D, Weigel A et al (2013) Metal binding is critical for the folding and function of laminin binding protein, Lmb of Streptococcus agalactiae. PLoS One.  https://doi.org/10.1371/journal.pone.0067517

Rainard P (2017) Mammary microbiota of dairy ruminants: fact or fiction? Vet Res 48:25. https://doi.org/10.1186/s13567-017-0429-2 PubMed DOI PMC

Rato MG, Bexiga R, Nunes SF et al (2008) Molecular epidemiology and population structure of bovine Streptococcus uberis. J Dairy Sci 91:4542–4551. https://doi.org/10.3168/jds.2007-0907 PubMed DOI

Reinoso EB, Lasagno MC, Dieser SA, Odierno LM (2011) Distribution of virulence-associated genes in Streptococcus uberis isolated from bovine mastitis. FEMS Microbiol 318:183–188. https://doi.org/10.1111/j.1574-6968.2011.02258.x DOI

Rocha CL, Fischetti VA (1999) Identification and characterization of a novel fibronectin-binding protein on the surface of group A streptococci. Infect Immun 67:2720–2728. https://doi.org/10.1128/iai.67.6.2720-2728.1999 PubMed DOI PMC

Rosey EL, Lincoln RA, Ward PN et al (1999) PauA: a novel plasminogen activator from Streptococcus uberis. FEMS Microbiol Lett 180:353–353. https://doi.org/10.1111/j.1574-6968.1999.tb08818.x PubMed DOI

Schaufuss P, Sting R, Schaeg W, Blobel H (1989) Isolation and characterization of hyaluronidase from Streptococcus uberis. Zentralblatt Fur Bakteriol 271:46–53. https://doi.org/10.1016/S0934-8840(89)80052-0 DOI

Schedin P, Mitrenga T, McDaniel S, Kaeck M (2004) Mammary ECM composition and function are altered by reproductive state. Mol Carcinog 41:207–220. https://doi.org/10.1002/mc.20058 PubMed DOI

Schubert A, Zakikhany K, Pietrocola G et al (2004) The fibrinogen receptor FbsA promotes adherence of Streptococcus agalactiae to human epithelial cells. Infect Immun 72:6197–6205. https://doi.org/10.1128/IAI.72.11.6197-6205.2004 PubMed DOI PMC

Severin A, Nickbarg E, Wooters J et al (2007) Proteomic analysis and identification of Streptococcus pyogenes surface-associated proteins. J Bacteriol 189:1514–1522. https://doi.org/10.1128/JB.01132-06 PubMed DOI

Shafeeq S, Kuipers OP, Kloosterman TG (2013) The role of zinc in the interplay between pathogenic streptococci and their hosts. Mol Microbiol 88:1047–1057. https://doi.org/10.1111/mmi.12256 PubMed DOI

Shimazaki KI, Kawai K (2017) Advances in lactoferrin research concerning bovine mastitis. Biochem Cell Biol 95:69–75 DOI

Shome BR, Bhuvana M, Mitra SD et al (2012) Molecular characterization of Streptococcus agalactiae and Streptococcus uberis isolates from bovine milk. Trop Anim Health Prod 44:1981–1992. https://doi.org/10.1007/s11250-012-0167-4 PubMed DOI

Singh B, Fleury C, Jalalvand F, Riesbeck K (2012) Human pathogens utilize host extracellular matrix proteins laminin and collagen for adhesion and invasion of the host. FEMS Microbiol Rev 36:1122–1180. https://doi.org/10.1111/j.1574-6976.2012.00340.x PubMed DOI

Smith AJ, Ward PN, Field TR et al (2003) MtuA, a lipoprotein receptor antigen from Streptococcus uberis, is responsible for acquisition of manganese during growth in milk and is essential for infection of the lactating bovine mammary gland. Infect Immun 71:4842–4849. https://doi.org/10.1128/IAI.71.9.4842-4849.2003 PubMed DOI PMC

Smith KL, Todhunter DA, Schoenberger PS (1985) Environmental pathogens and intramammary infection during the dry period. J Dairy Sci 68:402–417. https://doi.org/10.3168/jds.S0022-0302(85)80838-9 DOI

Sommer P, Gleyzal C, Guerret S et al (1991) Induction of a putative laminin-binding protein of Streptococcus gordonii in human infective endocarditis. Infect Immun 60:360–365. https://doi.org/10.1128/iai.60.2.360-365.1992 DOI

Spellerberg B, Rozdzinski E, Martin S et al (1999) Lmb, a protein with similarities to the LraI adhesin family, mediates attachment of Streptococcus agalactiae to human laminin. Infect Immun 67:871–878. https://doi.org/10.1128/iai.67.2.871-878.1999 PubMed DOI PMC

Talay SR, Valentin-Weigand P, Jerlstrom PG et al (1992) Fibronectin-binding protein of Streptococcus pyogenes: sequence of the binding domain involved in adherence of streptococci to epithelial cells. Infect Immun 60:3837–3844. https://doi.org/10.1128/iai.60.9.3837-3844.1992 PubMed DOI PMC

Tamilselvam B, Almeida RA, Dunlap JR, Oliver SP (2006) Streptococcus uberis internalizes and persists in bovine mammary epithelial cells. Microb Pathog 40:279–285. https://doi.org/10.1016/j.micpath.2006.02.006 PubMed DOI

Tamura GS, Hull JR, Oberg MD, Castner DG (2006) High-affinity interaction between fibronectin and the group B streptococcal C5a peptidase is unaffected by a naturally occurring four-amino-acid deletion that eliminates peptidase activity. Infect Immun 74:5739–5746. https://doi.org/10.1128/IAI.00241-06 PubMed DOI PMC

Tassi R, McNeilly TN, Fitzpatrick JL et al (2013) Strain-specific pathogenicity of putative host-adapted and nonadapted strains of Streptococcus uberis in dairy cattle. J Dairy Sci 96:5129–5145. https://doi.org/10.3168/jds.2013-6741 PubMed DOI

Tassi R, McNeilly TN, Sipka A, Zadoks RN (2015) Correlation of hypothetical virulence traits of two Streptococcus uberis strains with the clinical manifestation of bovine mastitis. Vet Res 46:1–12. https://doi.org/10.1186/s13567-015-0268-y DOI

Tedde V, Rosini R, Galeotti CL (2016) Zn DOI

Tenenbaum T, Bloier C, Adam R et al (2005) Adherence to and invasion of human brain microvascular endothelial cells are promoted by fibrinogen-binding protein FbsA of Streptococcus agalactiae. Infect Immun 73:4404–4409. https://doi.org/10.1128/IAI.73.7.4404-4409.2005 PubMed DOI PMC

Tenenbaum T, Spellerberg B, Adam R et al (2007) Streptococcus agalactiae invasion of human brain microvascular endothelial cells is promoted by the laminin-binding protein Lmb. Microbes Infect 9:714–720. https://doi.org/10.1016/j.micinf.2007.02.015 PubMed DOI

Terao Y, Kawabata S, Kunitomo E et al (2001) Fba, a novel fibronectin-binding protein from Streptococcus pyogenes, promotes bacterial entry into epithelial cells, and the fba gene is positively transcribed under the Mga regulator. Mol Microbiol 42:75–86. https://doi.org/10.1046/j.1365-2958.2001.02579.x PubMed DOI

Terao Y, Kawabata S, Kunitomo E et al (2002) Novel laminin-binding protein of Streptococcus pyogenes, Lbp, is involved in adhesion to epithelial cells. Infect Immun 70:993–997. https://doi.org/10.1128/IAI.70.2.993 PubMed DOI PMC

Thomas LH, Haider W, Hill AW, Cook RS (1994) Pathologic findings of experimentally induced Streptococcus uberis infection in the mammary gland of cows. Am J Vet Res 55:1723–1728 PubMed

Todhunter DA, Smith KL, Schoenberger PS (1985) In Vitro growth of mastitis associated streptococci in bovine mammary secretions. J Dairy Sci 68:2337–2346. https://doi.org/10.3168/jds.S0022-0302(85)81108-5 PubMed DOI

Varhimo E, Varmanen P, Fallarero A et al (2011) Alpha- and β-casein components of host milk induce biofilm formation in the mastitis bacterium Streptococcus uberis. Vet Microbiol 149:381–389. https://doi.org/10.1016/j.vetmic.2010.11.010 PubMed DOI

Walker MJ, Barnett TC, McArthur JD et al (2014) Disease manifestations and pathogenic mechanisms of group A Streptococcus. Clin Microbiol Rev 27:264–301. https://doi.org/10.1128/CMR.00101-13 PubMed DOI PMC

Ward PN, Field TR, Ditcham WG et al (2001) Identification and disruption of two discrete loci encoding hyaluronic acid capsule biosynthesis genes hasA, hasB, and hasC in Streptococcus uberis. Infect Immun 69:392–399. https://doi.org/10.1128/IAI.69.1.392-399.2001 PubMed DOI PMC

Ward PN, Holden TG, Leigh JA et al (2009) Evidence for niche adaptation in the genome of the bovine pathogen Streptococcus uberis. BMC Genomics 10:1–17. https://doi.org/10.1186/1471-2164-10-54 DOI

Weinberg E (2012) Antibiotic properties and application of lactoferrin. Front Med Chem 43:723. https://doi.org/10.14894/faruawpsj.43.7_723

Wente N, Klocke D, Paduch JH et al (2019) Associations between Streptococcus uberis strains from the animal environment and clinical bovine mastitis cases. J Dairy Sci 102:9360–9369. https://doi.org/10.3168/jds.2019-16669 PubMed DOI

Weston BF, Brenot A, Caparon MG (2009) The metal homeostasis protein, Lsp, of Streptococcus pyogenes is necessary for acquisition of zinc and virulence. Infect Immun 77(7):2840

Yi L, Wang Y, Ma Z et al (2013) Contribution of fibronectin-binding protein to pathogenesis of Streptococcus equi ssp. zooepidemicus. Pathog Dis 67:174–183. https://doi.org/10.1111/2049-632X.12029 PubMed DOI

Yinduo JI, McLandsborough L, Kondagunta A, Cleary PP (1996) C5a peptidase alters clearance and trafficking of group A streptococci by infected mice. Infect Immun 64:503–510. https://doi.org/10.1128/iai.64.2.503-510.1996 DOI

Young W, Hine BC, Wallace OAM et al (2015) Transfer of intestinal bacterial components to mammary secretions in the cow. PeerJ 3:e888. https://doi.org/10.7717/peerj.888 PubMed DOI PMC

Yuan Y, Dego OK, Chen X et al (2014) Short communication: conservation of Streptococcus uberis adhesion molecule and the sua gene in strains of Streptococcus uberis isolated from geographically diverse areas. J Dairy Sci 97:7668–7673. https://doi.org/10.3168/jds.2013-7637 PubMed DOI

Zadoks RN, Gillespie BE, Barkema HW et al (2003) Clinical, epidemiological and molecular characteristics of Streptococcus uberis infections in dairy herds. Epidemiol Infect 130:335–349. https://doi.org/10.1017/S0950268802008221 PubMed DOI PMC

Zadoks RN, Middleton JR, McDougall S. Katholm J, Schukken YH (2011) Molecular epidemiology of mastitis pathogens of dairy cattle and comparative relevance to humans. J Mammary Gland Biol Neoplasia 16(4):357–372

Zadoks RN, Tikofsky LL, Boor KJ (2005) Ribotyping of Streptococcus uberis from a dairy’s environment, bovine feces and milk. Vet Microbiol 109:257–265. https://doi.org/10.1016/j.vetmic.2005.05.008 PubMed DOI

Zhang Y-M, Shao Z-Q, Wang J et al (2014) Prevalent distribution and conservation of Streptococcus suis Lmb protein and its protective capacity against the Chinese highly virulent strain infection. Microbiol Res 169:395–401. https://doi.org/10.1016/j.micres.2013.09.007 PubMed DOI

Zhao X, Lacasse P (2008) Mammary tissue damage during bovine mastitis: causes and control. J Anim Sci 86:57–65 DOI