Curr Microbiol (2016) 72:377–382

DOI 10.1007/s00284-015-0958-8

Control of Bovine Mastitis: Old and Recent Therapeutic

Received: 20 October 2015 / Accepted: 30 October 2015 / Published online: 19 December 2015
Ó Springer Science+Business Media New York 2015

Abstract Mastitis is defined as the inflammatory decreased milk production, decreased milk quality,
response resulting of the infection of the udder tissue and it increased culling, loss of premiums, pre-term drying-off,
is reported in numerous species, namely in domestic dairy animal welfare aspects, and other associated health prob-
animals. This pathology is the most frequent disease of lems [35]. Numerous pathogens are responsible for mastitis
dairy cattle and can be potentially fatal. Mastitis is an with the majority of infections caused by the staphylococci,
economically important pathology associated with reduced streptococci, and enterobacteria. There are two types of
milk production, changes in milk composition and quality, mastitis, clinical and subclinical infections, and depending
being considered one of the most costly to dairy industry. on the primary reservoir and mode of transmission this
Therefore, the majority of research in the field has focused pathology can be contagious or environmental. The main
on control of bovine mastitis and many efforts are being contagious microorganisms are Staphylococcus aureus and
made for the development of new and effective anti-mas- Streptococcus agalactiae, being their main source the
titis drugs. Antibiotic treatment is an established compo- mammary gland of infected cows. On the other hand, the
nent of mastitis control programs; however, the continuous primary source of environmental mastitis pathogens is the
search for new therapeutic alternatives, effective in the habitat of the cow. Streptococcus uberis, Escherichia coli,
control and treatment of bovine mastitis, is urgent. This and Klebsiella spp. are examples of microorganisms
review will provide an overview of some conventional and included in this group [8]. Due to the predominance of
emerging approaches in the management of bovine masti- infectious mastitis and to the importance of the use of
tis’ infections. antimicrobial agents in the treatment and control of this
pathology, this microbial infection continues to deserve the
attention of several researchers and then continues to be a
Introduction subject of investigation by several groups. Therefore, this
review will discuss and focus on old and novel anti-mastitis
Bovine mastitis is the most costly pathology concerning strategies that have recently been explored.
dairy industry. The economic damages resulting of these
infections are related with direct and indirect losses. The Antibiotics
direct losses include the costs of treatment, discarded milk,
herdsman’s time, fatalities, and the costs associated with As referred, in the dairy industry, mastitis infections are the
repeated cases of mastitis. The indirect ones include the main cause of the usage of antibiotics. Nowadays, antibi-
otic therapy (such as natural or synthetic penicillins) is the
main strategy for mastitis treatment. However, beyond the
& Fernanda Gomes costs of its use, the emergence of resistance and the non-
fernandaisabel@deb.uminho.pt responsiveness of cattle to antibiotics has become a critical
1 issue. The overuse and misuse of antibiotics in bovine
LIBRO – Laboratório de Investigação em Biofilmes Rosário
Oliveira, CEB, Center of Biological Engineering, University mastitis may represent a serious problem related with the
of Minho, Campus de Gualtar, 4710-057 Braga, Portugal emergence of resistance and the entrance of resistant

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378 F. Gomes, M. Henriques: Control of Bovine Mastitis: Old and Recent Therapeutic Approaches

bacteria in food chain [49]. Taking this into account, mastitis’ pathogens. However, they also defend that more
antibiotic administration is strictly controlled by veteri- investigations need to be done namely, in terms of phar-
narians in the Nordic countries [46]. In addition, bacteria, maco-kinetics and pharmaco-dynamics, as well as studies
which are able to reside intracellularly, within the mam- concerning the administration of phages into intramam-
mary gland, and to form abscesses, are more difficult to mary tissues, aiming to ‘‘exploit phages to their full
combat due to the restriction of their contact with antibi- potential’’ [4]. Kwiatek et al. isolated a new virulent phage
otics. This is the case of S. aureus where the percentage of (MSA6) from a cow with mastitis, which presented a wide
cure using currently approved antibiotics (e.g., pirlimycin) lytic spectrum against staphylococcal strains of bovine
is approximately 10–30 %. Bannerman and Wall [3] con- origin. This polyvalent nature of MSA6 is crucial for their
cluded that therapies available for the treatment of mastitis potential use as universal anti-staphylococcal agent.
caused by S. aureus remain suboptimal and therefore Moreover, taking into consideration several features pre-
inefficacious. Moreover, the use of antibiotics has other sented by MSA6, this phage is similar to others formerly
disadvantages, as for example the presence of their residues used with success in bacteriophage therapy [27]. Every-
in the milk which is used for human consumption and thing indicates its possible use in several staphylococci
represents a concern to consumers. Therefore, it is urgent infections including bovine mastitis. Dias et al. [15] iso-
for the search of new antimicrobial therapies, namely non- lated that bacteriophages able to infect S. aureus from
antibiotics alternatives in order to minimize their use in mastitis-positive cows. These phages presented several
foodborne animals. Moreover, biofilm formation has been features critical to their use as phage therapy, namely wide
seen as one of the main factors contributing to antibiotic range of host, high lytic activity, and thermostability. In
resistance and recurrent mastitis infections [33]. Atulya addition, Fenton et al. [18] tested bacteriophage-derived
et al. studied the effect of milk composition on biofilm peptidase; CHAPK against S. aureus isolated from mastitis-
formation of some of the major mastitis pathogens, and infected cows. This study demonstrated the potential use of
described that pH was one of the factors that affected CHAPK as prophylactic and therapeutic measures of mas-
biofilm formation presenting a negative correlation. Once titis infections. CHAPK was effective against biofilms
current therapy is based on the use of acidic antibiotics, the either by preventing biofilm formation or by disrupting
authors suggested the administration of pH enhancing established biofilms of staphylococci strains associated
agents with the objective of reduce biofilm formation and with bovine mastitis. Basdew and Laing [5] tested some
consequently long-lasting infections [2]. All these limita- phages sensitivity to several simulated stresses. Sabp-P1,
tions presented by the antibiotics urged the search for new Sabp-P2, and Sabp-P3 were the less sensitive to the stresses
antimicrobial agents effective against mastitis pathogens. tested in vitro and therefore demonstrated to be the
Some of these alternatives are listed below. favorites to future in vivo experiments and to future use as
therapeutic strategy to treat mastitis-infected cows.
Bacteriophages Although still with some limitations, in general, bacterio-
phage therapy seems to be a serious candidate to antibiotic
Bacteriophage therapy can be a possible alternative to alternatives to be used in the future control and treatment
antibiotics in the fight against mastitis infections. Bacte- of bovine mastitis.
riophages are virus able to infect and kill bacteria [11].
Phages were demonstrated to be determinants as new Vaccination
antimicrobial agents for veterinary applications. Phage K is
an anti-staphylococcus phage, with lytic and antimicrobial During decades an effective vaccine for the prevention of
action and has been used as prophylactic measure in bovine mastitis was searched. However, the ‘‘miraculous’’
infections caused by S. aureus. However, to be used as vaccine remains elusive. Some vaccines were developed
therapeutic strategy for mastitis it must be active into the against S. aureus mastitis but all presented limited efficacy.
bovine mammary gland and when in contact with raw milk. The improper immunization schedules, ineffective adju-
This constitutes a disadvantage of phage K that was vant formulation, and the limited range of protection are
inhibited by natural milk and udder secretions [31]. Gill some of the causes of their ineffectiveness. This last point
et al. [20] also tested the efficacy of phage K against S. is crucial for the formulation of vaccines. It is important to
aureus. Once again, phage therapy presented several lim- find a vaccine capable of protecting against a wide range of
itations such as degradation/inactivation of phage by milk strains since multiple strains can be present within a herd
and its components (whey proteins) and by the immune and within an individual cow [3]. Due to its endemic nat-
system. Although the results were presented by the previ- ure, the large number of microorganisms that can cause the
ous studies, some researchers defend that bacteriophage disease, and the ubiquity of these pathogens, bovine mas-
therapy might be a valid alternative weapon against titis cannot be completely eradicated. Therefore, different

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F. Gomes, M. Henriques: Control of Bovine Mastitis: Old and Recent Therapeutic Approaches 379

strategies/vaccines are necessary in different countries in oxide)-nanoparticles were able to inhibit S. aureus, and in
order to respond to the specific requirement of an indi- general could be used in the treatment and prevention of
vidual country or segment of the dairy industry. Nowadays, bovine mastitis. In addition to the low price, safety NO-
vaccination became an important area in mastitis control nanoparticles can be an alternative to overcome the prob-
strategies and the implementation of an effective control lem of bacterial resistance development [10]. Berni et al.
protocol is becoming urgent [4]. Some vaccines for S. [7] tested violacein nanoparticles against bovine mastitis.
aureus were tested but their effect depends of several Violacein was considered a powerful antibactericidal agent
factors such as the type of vaccine used, the age of the cow, and its nanoparticles were more efficient against S. aureus
and environmental conditions [23, 34]. As example, bac- than the free agent. In conclusion, antimicrobial agents
terins made from killed bacteria were not effective in the encapsulated in nanoparticles and consequently the con-
prevention of new infections of S. aureus. When using a trolled drug delivery are among the potential strategies to
toxoid as bacterin adjuvant, a higher protective effect was control and prevent bovine mastitis infections.
observed. DNA and recombinant protein vaccines were
developed in alternative to conventional bacterin and as Cytokines
antibiotic therapy and proved to be active in protecting
mammary glands against S. aureus infections [41, 43, 51]. The emergence of antibiotic resistance has prompted the
Seegers et al. [39] demonstrated that when E. coli vacci- investigation of the immunotherapeutic use of recombinant
nation was used in the case of environmental mastitis a cytokines in the treatment of bovine mastitis. Cytokines are
higher annual benefit per cow was achieved in comparison small proteins that have an important role in cell signaling.
with a non-vaccine approach. Moreover, already in the 90s, Some cytokines (recombinant bovine cytokines, such as
DeGraves and Fetrow [14] also drew attention to the pos- IL-2, IFN-c, and TNF-a) demonstrated to be responsible for
sible reduction in the losses per cow after immunization. stimulating innate and acquired immunity in mammary
E. coli J5 is one existing vaccine for coliform mastitis and gland. However, this enhanced immunity was not enough
is composed of whole antigens derived from J5 mutant to prevent or treat bovine mastitis. Nevertheless, when
strain of E. coli. This vaccine showed some efficacy and combined with antibiotics, there was an additive effect
proved to be able to reduce the number and severity of being possible their use as adjuvant mastitis therapy [1].
coliform mastitis by 70–80 % [12, 50]. There are no vac-
cines available to prevent mastitis caused by K. pneumo- Natural Compounds
niae [44]. The mechanisms inherent to the spontaneous
cure that occurs in mild cases of subclinical mastitis can be Plant-Derived Antimicrobials
exploited to the production of new vaccines [36, 37] and
therefore the research in this area continues. As mentioned before, there is an urgent need for alterna-
tives to antibiotics for controlling bovine mastitis. Plants
Nanoparticles are promising sources of new biologically active agents
with antimicrobial action. Moreover, plant-derived drugs
Over the last few years, nanoparticles drew attention of have the advantage of not inducing resistance after pro-
some investigation groups since these structures can be longed exposure [16, 32]. Some examples of plant-derived
used as delivery vehicles for antimicrobial agents. Several natural compounds are diterpenes. Fonseca et al. tested
researchers demonstrated that nanoparticles can have three diterpenes: manool, ent-kaurenoic acid, and ent-
potential use in biomedical applications, namely on bovine copalic acid against several bovine mastitis pathogens. Ent-
mastitis infections. As example, silver nanoparticles copalic acid (CA) was the most active against most of the
showed to inhibit S. aureus isolated from subclinical microorganisms tested. Besides its antibacterial potential,
mastitis [13] and to be ideal for a highly cost-effective CA did not to cause a cytotoxic effect on human fibroblast
antimicrobial solution. The synergistic effect of silver cell line, so this fact encourages its possible use on bovine
nanoparticles and antibiotics was also evaluated, and a mastitis control and treatment [19]. Baskaran et al. [6] also
successful combination was obtained using antibiotics that investigated the antimicrobial activity of plant-derived
inhibit protein translation, such as erythromycin, in com- molecules on a wide array of bacterial mastitis pathogens
bination with silver nanoparticles against S. aureus [24]. in milk, namely, Streptococcus agalactiae, Streptococcus
On the other hand, Wang et al. [48] showed the potential of dysgalactiae, Streptococcus uberis, S. aureus, and E. coli.
tilmicosin-solid lipid nanoparticles against S. aureus. This in vitro study demonstrated that all plant-derived
Xuefeng [47] also reported amoxicillin nanoparticles as molecules (trans-cinnamaldehyde (TC), eugenol, car-
biologically active against S. aureus, E. coli, and S. vacrol, and thymol) were effective against all microor-
agalactiae. Cardozo et al. demonstrated that NO (nitric ganisms tested being TC the most effective. Since it was

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380 F. Gomes, M. Henriques: Control of Bovine Mastitis: Old and Recent Therapeutic Approaches

classified as safe by the United States Food and Drug general, all these studies showed positive results when
Administration and presented encouraging results against testing herbal extracts on mastitis-causing pathogens and
the major bacterial mastitis pathogens, it was suggested by allowed to suggest the potential use of several plants as a
Baskaran et al. [6] as a potential alternative/adjuvant to sustainable alternative treatment to replace antibiotics.
antibiotics in the prevention and treatment of bovine
mastitis. Additionally, ethanolic extracts of propolis (EEP), Animal-Derived Antimicrobials
which are a resinous mixture collected by honeybees from
parts of plants, were tested against S. aureus. These The use of immunomodulators, naturally produced by
extracts were biologically active against this mastitis mammals, such as lactoferrin, was appointed as potential
pathogen. However, when tested in cells cultivated in milk, non-antibiotic antimicrobial agents for treatment and pre-
a lower inhibitory effect was observed, concluding the vention of bovine mastitis. Lactoferrin is a glycoprotein
authors that milk component affect the antimicrobial found in several body secretions such as saliva, tears,
activity of EEP. Nevertheless, given their results and taking bronqueal mucus, and milk. This molecule exhibited an
into consideration that propolis-resistance appears to be a antibacterial effect against some major mastitis-causing
phenotype not easily selected, the authors suggested that pathogens namely E. coli, S. aureus, coagulase-negative
EEP might be a potential antimicrobial agent for mastitis staphylococci, Pseudomonas aeruginosa and K. pneumonia
control in vivo [38]. Khayatnouri and Topchi [25] tested [26]. Hafez et al. also isolated lactoferrin from bovine milk
the effect of monolaurin, a food grade glycerol monoester whey and tested its antimicrobial potential against S. aur-
of lauric acid found in coconut oil, on S. aureus isolates eus, E. coli, S. agalactiae, and P. aeruginosa. Lactoferrin
from bovine mastitis. Once again this compound demon- showed a significant inhibitory effect against all isolates
strated antibacterial effect against S. aureus. Gopinath et al. tested being more effective against E. coli and less effec-
[21] tested the effect of Tabernaemontana divaricata (L.) tive against S. aureus [22]. In general, their results are in
extracts on a panel of microorganisms responsible for accordance with the work of Kutila et al. [26] and also
bovine mastitis. A significant antibacterial effect was suggest the possible use of lactoferrin as antimicrobial and
observed on all bacteria studied. This preliminary research immunomodulator agent. b-Lactoglobulin is a protein
drew the attention to the possible use of natural compounds present in the whey of most mammals. When tested against
from Tabernaemontana divaricata (L.) as anti-mastitis several mastitis-causing pathogens this protein showed an
drug. In vitro tests conducted by Tolosa et al. [45] inhibitory effect on S. aureus and S. uberis. When tested in
demonstrated that crude extracts of two medicinal plants, combination with lactoferrin an additive effect was
Combertum molle and Commicarpus pedenculosus, observed against S. aureus. In addition to the increased
showed to have a good antimicrobial effect against S. combined effect of these two proteins, the fact that they
aureus isolated from bovine clinical mastitis. have different effect on different bacteria can
Moreover, extracts from twenty medicinal plants were enlarge/complement the spectrum of antimicrobial activity.
tested by Doss et al. against a wide array of infectious In addition, marine sponges are described as a source of
agents responsible for bovine mastitis. These extracts were new antimicrobial agents. Extracts of these sessile aquatic
active against the microorganisms tested [17, 30]. Centella animals presented inhibitory activity against several spe-
asiatica is another plant with a wide array of antimicrobial cies of coagulase-negative staphylococci (CNS) isolated
agents such as triterpenes. Crude extracts of this plant were from bovine mastitis cases. Among the marine sponges
tested against S. aureus isolated from mastitis-infected tested, Cinachyrella sp., Haliclona sp., and Petromica
cows. Ethanol extracts demonstrated to be biologically citrine were active against 61 % of the microorganisms
active against the strains tested. Although the authors studied, being the extracts of P. citrine the most effective
suggest more studies namely in vivo, they drew attention of against CNS strains [28].
the potential use of these compounds and consequently of
this plant as future alternative of antibiotics [42]. Plant Bacteria and Bacteria-Derived Antimicrobials
antimicrobial peptides (PAP) (c-thionin and thionin
Thi2.1), produced by bovine endothelial cells, were tested Natural compounds produced by bacteria and presenting
on intracellular S. aureus. These antimicrobial peptides antimicrobial action are also suggested by several
showed to be effective against this pathogen and therefore researchers as potential option for alternative antibiotics for
seem to be an attractive and potential antimicrobial the control and treatment of bovine mastitis. Weisella
approach to prevention and treatment of intracellular confusa (lactic acid bacteria) and its metabolites demon-
infections, namely intracellular S. aureus bovine mastitis. strated to be active against S. aureus and S. agalactiae [40].
Additionally to their antimicrobial activity, c-thionin and S. aureus is one of the most common etiological agents in
thionin Thi2.1, works as immunomodulators [29]. In mastitis of cows. The success rate of antibiotic treatment is

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F. Gomes, M. Henriques: Control of Bovine Mastitis: Old and Recent Therapeutic Approaches 381

low due to the ability of S. aureus to penetrate the mam- antimicrobials on major bacterial mastitis pathogens in vitro.
mary gland tissue and form abscesses. Taking this into J Dairy Sci 92(4):1423–1429
7. Berni E, Marcato PD, Nakazato G, Kobayashi RKT, Vacchi FI,
consideration, Bouchard et al. [9] tested live lactobacillus Umbuzeiro GA, Durán N (2013) Violacein/poly(e-caprolac-
casei as mammary probiotics. In fact, these bacteria were tone)/chitosan nanoparticles against bovine mastistis: Antibacte-
able to prevent the internalization of S. aureus into mam- rial and ecotoxicity evaluation. J Phys 429:012030
mary epithelial cells and therefore are appointed as possi- 8. Bogni C, Odierno L, Raspanti C, Giraudo J, Larriestra A, Reinoso
E, Lasagno M, Ferrari M, Ducrós E, Frigerio C, Bettera S, Pel-
ble strategy to reduce chronicity and recurrence of S. legrino M, Frola I, Dieser S, Vissio C (2011) War against mas-
aureus mastitis infections. titis: current concepts on controlling bovine mastitis Pathogens.
In: Méndez-Vilas A (ed) Science against microbial pathogens:
communicating current research and technological advances.
World Scientific, Singapore, pp 483–494
9. Bouchard DS, Rault L, Berkova N, Le Loir Y, Even S (2013)
Conclusions Inhibition of Staphylococcus aureus invasion into bovine mam-
mary epithelial cells by contact with live Lactobacillus casei.
Currently, the administration of antibiotics is the most Appl Environ Microbiol 79(3):877–885
common method of treatment of bovine mastitis. However, 10. Cardozo VF, Lancheros CA, Narciso AM, Valereto EC,
Kobayashi RK, Seabra AB, Nakazato G (2014) Evaluation of
this kind of strategy has some disadvantages including low
antibacterial activity of nitric oxide-releasing polymeric particles
cure rate, increasing occurrence of resistance, and the against Staphylococcus aureus and Escherichia coli from bovine
presence of antibiotics residues in the milk. Therefore, a mastitis. Int J Pharm 473(1–2):20–29
wide array of alternatives to antibiotics was investigated by 11. Chibani-Chennoufi S, Dillmann ML, Marvin-Guy L, Rami-Sho-
jaei S, Brüssow H (2004) Lactobacillus plantarum bacteriophage
several groups of researchers in order to find an effective
LP65: a new member of the SPO1-like genus of the family
approach for management of bovine mastitis. Bacterio- Myoviridae. J Bacteriol 186:7069–7083
phages, vaccines, nanoparticles, cytokines, and natural 12. Crist WL, Harmon RJ, O’Leary J, McAllister AJ (1997) Mastitis
compounds from plants, animals, and bacteria are some and its control [online]
13. Dehkordi SH, Hosseinpour F, Kahrizangi AE (2011) An in vitro
examples of valid substitutes to antibiotics. In vitro studies
evaluation of antibacterial effect of silver nanoparticles on Sta-
showed encouraging results but more tests, namely in vivo, phylococcus aureus isolated from bovine subclinical mastitis. Afr
are still critical. J Biotechnol 10(52):10795–10797
14. DeGraves FJ, Fetrow J (1991) Partial budget analysis of vacci-
Acknowledgments F. Gomes acknowledge the financial support of nating dairy cattle against coliform mastitis with an Escherichia
the Portuguese Foundation for Science and Technology through the coli J5 vaccine. J Am Med Assoc 199:451
Grant SFRH/BPD/84488/2012 and for financial support to the CEB 15. Dias RS, Eller MR, Duarte VS, Pereira ÂL, Silva CC, Mantovani
research center. HC, Oliveira LL, Silva Ede A, De Paula SO (2013) Use of phages
against antibiotic-resistant Staphylococcus aureus isolated from
Compliance with Ethical Standards bovine mastitis. J Anim Sci 91(8):3930–3939
16. Domadia P, Swarup S, Bhunia A, Sivaraman J, Dasgupta D
Conflicts of interest None. (2007) Inhibition of bacterial cell division protein FtsZ by cin-
namaldehyde. Biochem Pharmacol 74:831–840
17. Doss A, Mubarack HM, Vijayasanthi M, Venkataswamy R
(2012) In vitro antibacterial activity of certain wild medicinal
References plants against bovine mastitis isolated contagious pathogens.
Asian J Pharm Clin Res 5(2):90–93
1. Alluwaimi AM (2004) The cytokines of bovine mammary gland: 18. Fenton M, Keary R, McAuliffe O, Ross RP, O’Mahony J, Coffey
prospects for diagnosis and therapy. Res Vet Sci 77(3):211–222 A (2013) Bacteriophage-derived peptidase CHAPK eliminates
2. Atulya M, Mathew AJ, Rao JV, Rao CM (2014) Influence of milk and prevents staphylococcal biofilms. Int J Microbiol 2013:
components in establishing biofilm mediated bacterial mastitis 625341
infections in cattle: a fractional factorial approach. Res Vet Sci 19. Fonseca AP, Estrela FT, Moraes TS, Carneiro LJ, Bastos JK,
96:25–27 Santos RA, Ambrósio SR, Martins CHG, Veneziani RCS (2013)
3. Bannerman DD, Wall RJ (2005) A novel strategy for the pre- In vitro antimicrobial activity of plant-derived diterpenes against
vention of Staphylococcus aureus-induced mastitis in dairy cows. bovine mastitis bacteria. Molecules 18:7865–7872
Information Systems for Biotechnology (isb) news report, 1–4 20. Gill JJ, Pacan JC, Carson ME, Leslie KE, Griffiths MW, Sabour
4. Basdew IH, Laing MD (2011) Mini-review: biological control of PM (2006) Efficacy and pharmacokinetics of bacteriophage
bovine mastitis using bacteriophage therapy. In: Méndez-Vilas A therapy in treatment of subclinical Staphylococcus aureus mas-
(ed) Science against microbial pathogens: communicating current titis in lactating dairy cattle. Antimicrob Agents Chemother
research and technological advances. World Scientific, Singa- 50(9):2912
pore, pp 386–393 21. Gopinath SM, Suneetha TB, Mruganka VD, Ananda S (2011)
5. Basdew IH, Laing MD (2014) Stress sensitivity assays of bac- Evaluation of antibacterial activity of Tabernaemontana divari-
teriophages associated with Staphylococcus aureus, causal cata (L.) leaves against the causative organisms of bovine mas-
organism of bovine mastitis. Afr J Microbiol Res 8(2):200–210 titis. Int J Res Phytochem Pharmacol 1(4):211–213
6. Baskaran SA, Kazmer GW, Hinckley L, Andrew SM, Venkita- 22. Hafez SM, Ismael AB, Mahmoud MB, Elaraby AA (2013)
narayanan K (2009) Antibacterial effect of plant-derived Development of new strategy for non-antibiotic therapy: bovine

123
382 F. Gomes, M. Henriques: Control of Bovine Mastitis: Old and Recent Therapeutic Approaches

lactoferrin has a potent antimicrobial and immunomodulator 38. Santana HF, Barbosa AAT, Ferreira SO, Mantovani HC (2012)
effects. Adv Infect Dis 3:185–192 Bactericidal activity of ethanolic extracts of propolis against
23. Hoedemaker M, Korff B, Edler B, Emmert M, Bleckmann E Staphylococcus aureus isolated from mastitic cows. World J
(2001) Dynamics of Staphylococcus aureus infections during Microbiol Biotechnol 28(2):485–491
vaccination with an autogenous bacterin in dairy cattle. J Vet 39. Seegers H, Fourichon C, Beaudeau F (2003) Production effects
Med 48(5):373–383 related to mastitis and mastitis economics in dairy cattle herds.
24. Kazemi J, Ahmadi M, Saei HD, Adib hesami M (2014) Vet Res 34:475–491
Antibacterial effect of silver nanoparticles along with protein 40. Serna-Cock L, Enrı́quez-Valencia CE, Jiménez-Obando EM,
synthesis-inhibiting antibiotics on Staphylococcus aureus isolated Campos-Gaona R (2012) Effects of fermentation substrates and
from cattle mastitis. Biol J Microorg 2(8):15–22 conservation methods on the viability and antimicrobial activity
25. Khayatnouri MH, Topchi A (2013) Evaluation of antibacterial of Weissella confusa and its metabolites. Electron J Biotechnol
effect of monolaurin on Staphylococcus aureus isolated from 5(3):6
bovine mastitis. Afr J Pharm Pharmacol 7(19):1163–1166 41. Shkreta L, Talbot BG, Diarra MS, Lacasse P (2004) Immune
26. Kutila T, Pyörälä S, Kaartinen L, Isomäki R, Vahtola K, Myl- responses to a DNA/protein vaccination strategy against Sta-
lykoski L, Saloniemi H (2003) Lactoferrin and citrate concen- phylococcus aureus induced mastitis in dairy cows. Vaccine
trations at drying-off and during early mammary involution of 23:114–126
dairy cows. J Vet Med Series A 50(7):350–353 42. Taemchuay D, Rukkwamsuk T, Sakpuaram T, Ruangwises N
27. Kwiatek M, Parasion S, Mizak L, Gryko R, Bartoszcze M, Kocik (2009) Antibacterial activity of crude extracts of Centella asiat-
J (2012) Characterization of a bacteriophage, isolated from a cow ica against Staphylococcus aureus in bovine mastitis. Kasetsart
with mastitis, that is lytic against Staphylococcus aureus strains. Vet 19(3):119–128
Arch Virol 157:225–234 43. Talbot BG, Lacasse P (2005) Progress in the development of
28. Laport MS, Marinho PR, Santos OC, de Almeida P, Romanos mastitis vaccines. Livest Prod Sci 98:101–113
MT, Muricy G, Brito MA, Giambiagi-deMarval M (2012) 44. Tiwari J, Babra C, Tiwari HK, Williams V, De Wet S, Gibson J,
Antimicrobial activity of marine sponges against coagulase- Paxman A, Morgan E, Costantino P, Sunagar R, Isloor S, Hegde
negative staphylococci isolated from bovine mastitis. Vet NR, Mukkur T (2013) Trends in therapeutic and prevention
Microbiol 155(2–4):362–368 strategies for management of bovine mastitis: an overview.
29. Loeza-Ángeles H, López-Meza JE, Ochoa-Zarzosa A (2011) Vaccines Vaccin 4:2
Antimicrobial effects of plant defence peptides expressed by 45. Tolosa T, Wagaye H, Regassa F (2009) A study on in vitro
bovine endothelial cells on intracellular pathogens. Electron J antimicrobial effects of some selected plants on Staphylococcus
Biotechnol 14(5):1–1 aureus isolated from bovine clinical mastitis. Int J Vet Med
30. Mubarack HM, Doss AR, Dhanabalan R, Venkataswamy R 8(1):1–7
(2011) Activity of some selected medicinal plant extracts against 46. Valde JP, Lawson LG, Lindberg A, Agger JF, Saloniemi H,
bovine mastitis pathogens. J Anim Vet Adv 10(6):738–741 Østerås O (2004) Cumulative risk of bovine mastitis treatments in
31. O’Flaherty S, Coffey A, Meaney WJ, Fitzgerald GF, Ross RP Denmark, Finland, Norway and Sweden. Acta Vet Scand
(2005) Inhibition of bacteriophage K proliferation on Staphylo- 45:201–210
coccus aureus in raw bovine milk. Lett Appl Microbiol 47. Xuefeng Y (2009) Post-antibiotic effect of amoxicillin nanopar-
41:274–279 ticles against main pathogenic bacteria of bovine mastitis in vitro.
32. Ohno T, Kita M, Yamaoka Y, Imamura S, Yamamoto T, Mit- J Northwest Sci-Tech Univ Agric For 37(6):1–6
sufuji S, Kodama T, Kashima K, Imanishi J (2003) Antimicrobial 48. Wang XF, Zhang SL, Zhu LY, Xie SY, Dong Z, Wang Y, Zhou
activity of essential oils against Helicobacter pylori. Helicobacter WZ (2012) Enhancement of antibacterial activity of tilmicosin
8:207–215 against Staphylococcus aureus by solid lipid nanoparticles
33. Olson ME, Ceri H, Morck DW, Buret AG, Read RR (2002) in vitro and in vivo. Vet J 191(1):115–120
Biofilm bacteria: formation and comparative susceptibility to 49. White DG, McDermott PF (2001) Emergence and transfer of
antibiotics. Can J Vet Res 66(2):86–92 antibiotic resistance. J Dairy Sci 84(E. Suppl):E151–E155
34. Pereira UP, Oliveira DGS, Mesquita LR, Costa GM, Pereira LJ 50. Wilson DJ, González RN (2003) Vaccination strategies for
(2011) Efficacy of Staphylococcus aureus vaccines for bovine reducing clinical severity of coliform mastitis. Vet Clin North
mastitis: a systematic review. Vet Microbiol 148:117–124 Am Food Anim Pract 19:187–197
35. Petrovski KR, Trajcev M, Buneski G (2006) A review of the 51. Zecconi A, Binda E, Borromeo V, Piccinini R (2005) Relation-
factors affecting the costs of bovine mastitis. J South Afr Vet ship between some Staphylococcus aureus pathogenic factors and
Assoc 77:52–60 growth rates and somatic cell counts. J Dairy Res 72:203–208
36. Philpot WN, Nickerson SC (1999) Mastitis: counter attack.
Westfalia Surge LLC, Illinois
37. Ruegg PL (2009) Management of mastitis on organic and con-
ventional dairy farms. J Anim Sci 87:43–55

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