Endolysin NC5 improves early cloxacillin treatment in a mouse model of Streptococcus uberis mastitis.
Bovine mastitis
Cloxacillin
Endolysin
Mouse model
Penicillin
Streptococcus uberis
Journal
Applied microbiology and biotechnology
ISSN: 1432-0614
Titre abrégé: Appl Microbiol Biotechnol
Pays: Germany
ID NLM: 8406612
Informations de publication
Date de publication:
Dec 2024
Dec 2024
Historique:
received:
29
08
2023
accepted:
18
12
2023
revised:
07
12
2023
medline:
11
1
2024
pubmed:
11
1
2024
entrez:
11
1
2024
Statut:
ppublish
Résumé
Streptococcus uberis frequently causes bovine mastitis, an infectious udder disease with significant economic implications for dairy cows. Conventional antibiotics, such as cloxacillin, sometimes have limited success in eliminating S. uberis as a stand-alone therapy. To address this challenge, the study objective was to investigate the VersaTile engineered endolysin NC5 as a supplemental therapy to cloxacillin in a mouse model of bovine S. uberis mastitis. NC5 was previously selected based on its intracellular killing and biofilm eradicating activity. To deliver preclinical proof-of-concept of this supplemental strategy, lactating mice were intramammarily infected with a bovine S. uberis field isolate and subsequently treated with cloxacillin (30.0 μg) combined with either a low (23.5 μg) or high (235.0 μg) dose of NC5. An antibiotic monotherapy group, as well as placebo treatment, was included as controls. Two types of responders were identified: fast (n = 17), showing response after 4-h treatment, and slow (n = 10), exhibiting no clear response at 4 h post-treatment across all groups. The high-dose combination therapy in comparison with placebo treatment impacted the hallmarks of mastitis in the fast responders by reducing (i) the bacterial load 13,000-fold (4.11 ± 0.78 Δlog
Identifiants
pubmed: 38204128
doi: 10.1007/s00253-023-12820-w
pii: 10.1007/s00253-023-12820-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-12Subventions
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 1.S.236.20N
Informations de copyright
© 2024. The Author(s).
Références
Aldinger KA, Sokoloff G, Rosenberg DM, Palmer AA, Millen KJ (2009) Genetic variation and population substructure in outbred CD-1 mice: implications for genome-wide association studies. PLoS One 4:e4729. https://doi.org/10.1371/journal.pone.0004729
doi: 10.1371/journal.pone.0004729
pubmed: 19266100
pmcid: 2649211
Almeida JS, Iriabho EE, Gorrepati VL, Wilkinson SR, Grüneberg A, Robbins DE, Hackney JR (2012) ImageJS: personalized, participated, pervasive, and reproducible image bioinformatics in the web browser. J Pathol Inform 3:25. https://doi.org/10.4103/2153-3539.98813
doi: 10.4103/2153-3539.98813
pubmed: 22934238
pmcid: 3424663
Beal J, Farny NG, Haddock-Angelli T, Selvarajah V, Baldwin GS, Buckley-Taylor R, Gershater M, Kiga D, Marken J, Sanchania V, Sison A, Workman CT, iGEM Interlab Study Contributors (2020) Robust estimation of bacterial cell count from optical density. Commun Biol 3:512. https://doi.org/10.1038/s42003-020-01127-5
doi: 10.1038/s42003-020-01127-5
pubmed: 32943734
pmcid: 7499192
Becker SC, Roach DR, Chauhan VS, Shen Y, Foster-Frey J, Powell AM, Bauchan G, Lease RA, Mohammadi H, Harty WJ, Simmons C, Schmelcher M, Camp M, Dong S, Baker JR, Sheen TR, Doran KS, Pritchard DG, Almeida RA et al (2016) Triple-acting lytic enzyme treatment of drug-resistant and intracellular Staphylococcus aureus. Sci Rep 6:1–10. https://doi.org/10.1038/srep25063
doi: 10.1038/srep25063
Breyne K, Steenbrugge J, Demeyere K, Vanden Berghe T, Meyer E (2017) Preconditioning with lipopolysaccharide or lipoteichoic acid protects against Staphylococcus aureus mammary infection in mice. Front Immunol 8:1–16. https://doi.org/10.3389/fimmu.2017.00833
doi: 10.3389/fimmu.2017.00833
Breyne K, Steenbrugge J, Demeyere K, Lee CG, Elias JA, Petzl W, Smith DGE, Germon P, Meyer E (2018) Immunomodulation of host chitinase 3-like 1 during a mammary pathogenic Escherichia coli infection. Front Immunol 9:1143. https://doi.org/10.3389/fimmu.2018.01143
doi: 10.3389/fimmu.2018.01143
pubmed: 29892291
pmcid: 5985307
Burvenich C, Van Merris V, Mehrzad J, Diez-Fraile A, Duchateau L (2003) Severity of E. coli mastitis is mainly determined by cow factors. Vet Res 34:521–564. https://doi.org/10.1051/vetres:2003023
doi: 10.1051/vetres:2003023
pubmed: 14556694
Daniel A, Euler C, Collin M, Chahales P, Gorelick KJ, Fischetti VA (2010) Synergism between a novel chimeric lysin and oxacillin protects against infection by methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 54:1603–1612. https://doi.org/10.1128/AAC.01625-09
doi: 10.1128/AAC.01625-09
pubmed: 20086153
pmcid: 2849374
de Jong A, Garch FE, Simjee S, Moyaert H, Rose M, Youala M, Siegwart E, VetPath Study Group (2018) Monitoring of antimicrobial susceptibility of udder pathogens recovered from cases of clinical mastitis in dairy cows across Europe: VetPath results. Vet Microbiol 213:73–81. https://doi.org/10.1016/j.vetmic.2017.11.021
doi: 10.1016/j.vetmic.2017.11.021
pubmed: 29292007
Demon D, Breyne K, Schiffer G, Meyer E (2013) Short communication: antimicrobial efficacy of intramammary treatment with a novel biphenomycin compound against Staphylococcus aureus, Streptococcus uberis, and Escherichia coli-induced mouse mastitis. J dairy sci 96:7082–7087. https://doi.org/10.3168/jds.2013-7011
doi: 10.3168/jds.2013-7011
pubmed: 24054294
Ezzat Alnakip M, Quintela-Baluja M, Böhme K, Fernández-No I, Caamaño-Antelo S, Calo-Mata P, Barros-Velázquez J (2014) The immunology of mammary gland of dairy uminants between healthy and inflammatory conditions. J Vet Med 2014:1–31. https://doi.org/10.1155/2014/659801
doi: 10.1155/2014/659801
Festing MFW (2010) Inbred strains should replace outbred stocks in toxicology, safety testing and drug development. Toxicol Pathol 38:681–690. https://doi.org/10.1177/0192623310373776
doi: 10.1177/0192623310373776
pubmed: 20562325
Gerstmans H, Grimon D, Gutiérrez D, Lood C, Rodríguez A, van Noort V, Lammertyn J, Lavigne R, Briers Y (2020) A VersaTile-driven platform for rapid hit-to-lead development of engineered lysins. Sci Adv 6:1–12. https://doi.org/10.1126/sciadv.aaz1136
doi: 10.1126/sciadv.aaz1136
Günther J, Czabanska A, Bauer I, Leigh JA, Holst O, Seyfert HM (2016) Streptococcus uberis strains isolated from the bovine mammary gland evade immune recognition by mammary epithelial cells, but not of macrophages. Vet Res 1–14. https://doi.org/10.1186/s13567-015-0287-8
Gutiérrez D, Garrido V, Fernández L, Portilla S, Rodríguez A, Grilló MJ, García P (2020) Phage lytic protein LysRODI prevents staphylococcal mastitis in mice. Front Microbiol 11:1–13. https://doi.org/10.3389/fmicb.2020.00007
doi: 10.3389/fmicb.2020.00007
Ingman WV, Glynn DJ, Hutchinson MR (2015) Mouse models of mastitis – how physiological are they? Int Breastfeed J 10:12. https://doi.org/10.1186/s13006-015-0038-5
doi: 10.1186/s13006-015-0038-5
pubmed: 25848399
pmcid: 4386103
Johnzon CF, Dahlberg J, Gustafson AM, Waern I, Moazzami AA, Östensson K, Pejler G (2018) The effect of lipopolysaccharide-induced experimental bovine mastitis on clinical parameters, inflammatory markers, and the metabolome: a kinetic approach. Front Immunol 9:1487. https://doi.org/10.3389/fimmu.2018.01487
doi: 10.3389/fimmu.2018.01487
pubmed: 29988549
pmcid: 6026673
Kim D, Kim S, Kwon Y, Kim Y, Park H, Kwak K, Lee H, Lee JH, Jang KM, Kim D, Lee SH, Kang LW (2023) Structural insights for β-lactam antibiotics. Biomol Ther 31:141–147. https://doi.org/10.4062/biomolther.2023.008
doi: 10.4062/biomolther.2023.008
Klaas IC, Zadoks RN (2018) An update on environmental mastitis: challenging perceptions. Transbound Emerg Dis 65(Suppl 1):166–185. https://doi.org/10.1111/tbed.12704
doi: 10.1111/tbed.12704
pubmed: 29083115
Lipkens Z, Piepers S, De Vliegher S (2023) Impact of selective dry cow therapy on antimicrobial consumption, udder health, milk yield, and culling hazard in commercial dairy herds. MDPI Antibiot 12:5. https://doi.org/10.3390/antibiotics12050901
doi: 10.3390/antibiotics12050901
Liu G, Zhang S, Gao T, Mao Z, Shen Y, Pan Z, Guo C, Yu Y, Yao H (2022) Identification of a novel broad-spectrum endolysin, Ply0643, with high antibacterial activity in mouse models of streptococcal bacteriaemia and mastitis. Res Vet Sci 143:41–49. https://doi.org/10.1016/j.rvsc.2021.12.014
doi: 10.1016/j.rvsc.2021.12.014
pubmed: 34973538
Malyala P, Singh M (2008) Endotoxin limits in formulations for preclinical research. J Pharm Sci 97:2041–2044. https://doi.org/10.1002/jps.21152
doi: 10.1002/jps.21152
pubmed: 17847072
Martin KR, Wong HL, Witko-Sarsat V, Wicks IP (2021) G-CSF - a double edge sword in neutrophil mediated immunity. Semin Immunol 54:101516. https://doi.org/10.1016/j.smim.2021.101516
doi: 10.1016/j.smim.2021.101516
pubmed: 34728120
Messom G, Burvenich C, Roets E, Massart-Leën A, Heyneman R, Kremer W, Brand A (1993) Classification of newly calved cows into moderate and severe responders to experimentally induced Escherichia coli mastitis. J Dairy Sci 60:19–29. https://doi.org/10.1017/S002202990002731X
doi: 10.1017/S002202990002731X
Moliva MV, Campra N, Ibañez M, Cristofolini AL, Merkis CI, Reinoso EB (2022) Capacity of adherence, invasion and intracellular survival of Streptococcus uberis biofilm-forming strains. J Appl Microbiol 132:1751–1759. https://doi.org/10.1111/jam.15362
doi: 10.1111/jam.15362
pubmed: 34800320
Murray E, Draper LA, Ross RP, Hill C (2021) The advantages and challenges of using endolysins in a clinical setting. Viruses 13:4. https://doi.org/10.3390/v13040680
doi: 10.3390/v13040680
Notebaert S, Meyer E (2006) Mouse models to study the pathogenesis and control of bovine mastitis. A review. Vet Q 28:2–13. https://doi.org/10.1080/01652176.2006.9695201
doi: 10.1080/01652176.2006.9695201
pubmed: 16605156
Rainard P, Gilbert FB, Germon P (2022) Immune defenses of the mammary gland epithelium of dairy ruminants. Front Immunol 13:1–26. https://doi.org/10.3389/fimmu.2022.1031785
doi: 10.3389/fimmu.2022.1031785
Salamon H, Weizmann N, Nissim-eliraz E, Lysnyansky I, Shpigel NY (2023) Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis and Streptococcus uberis. Front Microbiol 14:1126896. https://doi.org/10.3389/fmicb.2023.1126896
doi: 10.3389/fmicb.2023.1126896
pubmed: 37032878
pmcid: 10080000
Schmelcher M, Powell AM, Becker SC, Camp MJ, Donovan DM (2012) Chimeric phage lysins act synergistically with lysostaphin to kill mastitis-causing Staphylococcus aureus in murine mammary glands. Appl Environ Microbiol 78:2297–2305. https://doi.org/10.1128/AEM.07050-11
doi: 10.1128/AEM.07050-11
pubmed: 22286996
pmcid: 3302589
Schmelcher M, Powell AM, Camp MJ, Pohl CS, Donovan DM (2015) Synergistic streptococcal phage λSA2 and B30 endolysins kill streptococci in cow milk and in a mouse model of mastitis. Appl Microbiol Biotechnol 99:8475–8486. https://doi.org/10.1007/s00253-015-6579-0
doi: 10.1007/s00253-015-6579-0
pubmed: 25895090
pmcid: 4573782
Schönborn S, Wente N, Paduch JH, Krömker V (2017) In vitro ability of mastitis causing pathogens to form biofilms. J Dairy Res 84:198–201. https://doi.org/10.1017/S0022029917000218
doi: 10.1017/S0022029917000218
pubmed: 28524019
Steenbrugge J, Bellemans J, Vander Elst N, Demeyere K, De Vliegher J, Perera T, De Wever O, Van Den Broeck W, De Spiegelaere W, Sanders NN, Meyer E (2022) One cisplatin dose provides durable stimulation of anti-tumor immunity and alleviates anti-PD-1 resistance in an intraductal model for triple-negative breast cancer. Oncoimmunology 11:2103277. https://doi.org/10.1080/2162402X.2022.2103277
doi: 10.1080/2162402X.2022.2103277
pubmed: 35898705
pmcid: 9311321
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
doi: 10.1016/j.micpath.2006.02.006
pubmed: 16678381
Thomas V, de Jong A, Moyaert H, Simjee S, El Garch F, Morrissey I, Marion H, Vallé M (2015) Antimicrobial susceptibility monitoring of mastitis pathogens isolated from acute cases of clinical mastitis in dairy cows across Europe: VetPath results. Int J Antimicrob Agents 46:13–20. https://doi.org/10.1016/j.ijantimicag.2015.03.013
doi: 10.1016/j.ijantimicag.2015.03.013
pubmed: 26003836
Vander Elst N, Breyne K, Steenbrugge J, Gibson AJ, Smith DGE, Germon P, Werling D, Meyer E (2020a) Enterobactin deficiency in a coliform mastitis isolate decreases its fitness in a murine model: a preliminary host–pathogen nteraction study. Front Vet Sci 7:1–11. https://doi.org/10.3389/fvets.2020.576583
doi: 10.3389/fvets.2020.576583
Vander Elst N, Linden SB, Lavigne R, Meyer E, Briers Y, Nelson DC (2020b) Characterization of the bacteriophage-derived endolysins PlySs2 and PlySs9 with in vitro lytic activity against bovine mastitis Streptococcus uberis. MDPI Antibiot 9:1–14. https://doi.org/10.3390/antibiotics9090621
doi: 10.3390/antibiotics9090621
Vander Elst N, Bellemans J, Steenbrugge J, Geeroms C, Breyne K, Piepers S, Toledo-Silva B, de Souza FN, Haesebrouck F, De Vliegher S, Meyer E (2023a) Priming of the murine mammary gland with Staphylococcus chromogenes IM reduces bacterial growth of Streptococcus uberis: a proof-of-concept study. Vet Res 54:1–8. https://doi.org/10.1186/s13567-023-01156-y
doi: 10.1186/s13567-023-01156-y
Vander Elst N, Bert J, Favoreel H, Lavigne R, Meyer E, Briers Y (2023b) Development of engineered endolysins with in vitro intracellular activity against streptococcal bovine mastitis-causing pathogens. Microb Biotechnol 00:1–20. https://doi.org/10.1111/1751-7915.14339
doi: 10.1111/1751-7915.14339
Woodward AP, Whittem T (2019) Physiologically based modelling of the pharmacokinetics of three beta-lactam antibiotics after intra-mammary administration in dairy cows. J Vet Pharmacol Ther 42:693–706. https://doi.org/10.1111/jvp.12812
doi: 10.1111/jvp.12812
pubmed: 31553070