Coagulase-positive staphylococci are a group of bacteria that, among other things, cause inflammation of the udder in cows (mastitis). The identification of the species of staphylococcus causing the inflammation is crucial for the success of the treatment process due to the individual characteristics of the strains and even the characteristics of the bacterial population in the herd. However, through evolution, staphylococci have developed a number of processes that make species identification difficult. Knowledge of the actual cause of inflammation enables the selection of appropriate therapy, but despite advanced diagnostic tech- niques, erroneous results still occur. In this review, we present the current knowledge of mainly resistance mechanisms and how they affect the drug resistance of microorganisms. We also highlight the difficulties in the diagnosis and treatment of bovine mastitis. Running title: Mastitis in cows caused by coagulase-producing staphylococci Keywords: mastitis, cows, diagnosis, Staphylococcus aureus, coagulase-positive Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Toruń, Toruń, Poland *Correspondence: Arkadiusz.firstname.lastname@example.org Full list of author information is available at the end of article 101 Grzeczka et al. Medical Journal of Cell Biology (2021) USA and Germany are similar, as they are at the level Introduction of 41.2% and 47.1%, respectively . On the other Bacteria of Staphylococcus were divided into co- hand, information showing this frequency in Brazil agulase-positive (CPS - Coagulase Possitive Staphy- is 74.07% . Staphylococcus aureus borderline re- lococci) and coagulase-negative (CNS - Coaugulase sistant to oxacillin, an antibiotic of the beta-lactam Negative Staphylococci). This division was due to group, is described. It is most likely related to a mu- the features of metabolism, parts of bacteria that tation in the gene blaZ or a change in the structure allow the production and secretion of an enzyme of PBP2 (Penicillin-binding protein) . These data called coagulase into the external environment. demonstrate the continuing variability of microbes By infecting the cow’s udder, staphylococcal bacte- in terms of antibiotic resistance. Staphylococcus au- ria initiate a reaction of the immune system. First, reus regularly resistant to beta-lactam antibiotics is there is a non-specific response of the organism in called MRSA (Methicillin-resistant Staphylococcus the form of increasing the temperature of the ud- aureus). The pathogenicity of MRSA is guaranteed der. Then the pathogen is attacked by the appearing by the presence of the gene in the mobile part of the granular cells in the place of demand thanks to the bacterial genotype mecA. The presence of this gene concentration gradient of chemoattractants such as in coagulase-positive staphylococci is region-spe- the CXCL8 chemokine or by the use of cell surface cific. In South-West Asia, the values presented by receptors by, for example, leukotriene B4 (LTB4) the authors are much higher than in European for the recruitment of granulocytes . Excessive countries. One such country is Iran where the pres- amount of leukocytes increases the number of so- ence of the gene mecA has been shown to be 35% matic cells in milk - making it possible to notice in- . Another example is the study from Pakistan fection. The infected cow becomes a reservoir of the where the gen mecA occurred with a frequency of pathogen in the herd, making it possible to transmit 30% . For comparison, in Germany and Italy its bacteria to the other cows. incidence is much lower (6.9% and 5.9%, respec- Discussion of the problem tively) . A higher rate for European countries is In the structure of their walls, staphylococci pos- reported in a study on the prevalence of the mecA sess proteins (FnBPA - fibronectin-bindin protein gene in Greece, which was 10% there . MRSA is A) that have a role in the adhesion process, but Fn- characterized by a specific configuration of PBP2, a BPA also has a variable affinity for fibrinogen . cell wall protein that has a low affinity for penicil- In addition to proteins such as FnBPA, coagulase lin. However, also in this case there is considerable also acts to bind fibrinogen. The described activity lability in resistance to the individual antibiotics of of this enzyme comes down to the formation of a the beta-lactam panel. This is indicated by the data capsule around the bacteria. The capsule protects from the study Fergestad ME (2020) talking about the bacterial cell against the activity of the immune the highest resistance to cefacrin and cefaxin . system of the infected organism . Regulation of The resistance profile of staphylococcus aureus is coagulase production takes place in the region agr variable, as indicated by the conducted studies . however, as some studies indicate, there may be a Namely in one of the studies Mphahlele MP (2020) targeted inhibition of the activity of this part of the presents data on 2,862 samples from which 50 genotype in order to avoid the reaction of the im- Staphylococcus aureus were isolated. Each of them mune system of the infected organism . In addi- was resistant to at least one of the antibiotics to tion, a possibility of the formation of a biofilm by which they had been exposed. In contrast, 62% were staphylococci, a group of bacteria coated with pol- resistant to three or more categories of antibiotics. ysaccharide intercellular adhesin (PIA), makes it They were most often resistant to erythromycin difficult to treat infections with these microorgan- (62%), ampicillin (62%) and oxacillin (46%) . isms. Covering the tissue with biofilm is not only On the other hand, Bissong MAE (2020), analyzing beneficial due to the possibility of living close to the resistance of staphylococcus aureus, showed 39 epithelial cells, but it has also been proven that the isolates S. aureus from 289 microorganisms . In structure of the biofilm retains water and nutrients both of these studies, staphylococci were character- for bacterial cells . There are reports of the de- ized by high resistance to erythomycin (82% - Bis- gradable influence of the active form of artesunate song, 62% - Mphahlele), and in the case of Bissong - dihydroartemisinin, a widely used agent in the MAE work, there was high resistance to vancomycin treatment of malaria, on biofilm of the Staphylo- (80%) and tetracycline (76%). These data are worth coccus aureus . However, staphylococcus aureus comparing with the Egyptian report of much lower bases its antibiotic resistance on the production resistance of Staphylococcus aureus for antibiotics. of enzymes - beta-lacatamases. They are coded by Namely, resistance to erythromycin was 30.9%, to the gen blaZ. They are proteins that hydrolyze an- tetracycline 59.5% and to penicillin 64.3% . A tibiotics from the group of beta-lactam antibiotics. study by Shi C. (2021) presents the prevention and Reported frequency of occurrence of the blaZ is resistance profile of Staphylococcus aureus to an- variable depending on the region. The data for the tibacterial preparations. The study showed that 5 102 Grzeczka et al. Medical Journal of Cell Biology (2021) out of 15 used antibacterial agents were isolates of (71.5%) were coagulase-positive and the rest did Staphylococcus aureus possessed over 50% degree not clot in the plasma. However, these data may not of resistance. The bacteria that were the least sensi- be consistent with reality due to the facts presented tive turned out to be penicillin G (81.5%), sulfameth- in the study by Almeida K. (2018). This study shows oxazole (73.6%), trimethoprim (70.3%), oxacycline the percentage of false positive tests that diagnose (63%), and clindamycin (50.4%). It is worth adding the Staphylococcus aureus. Out of 408 samples, 32 that different results have been noticed in different Staphylococcus aureus strains were obtained after parts of the country regarding the average rate of a positive coagulase test and Sa442 PCR. However, resistance. The highest percentage of infections was after the latex agglutination test, the number of true recorded in the northern part of the country, while strains belonging to this species was reduced to 10, the lowest in the southern part. On the other hand, and 8 remained after passing the MALDI-TOF MS the incidence of Staphylococcus aureus in research test. Additionally, a RealPCR study was conducted samples was 36.8% . which reduced this number to 7. Most commonly, Other staphylococci, due to the significant domi- the coagulase-negative bacterium S. chromogenes nance of the Staphylococcus aureus in the percent- was misidentified as S. aureus . Gene sequenc- age of infections, were referred to as Non-Aureus ing in diagnostics allows for almost 100% determi- Staphylococci (NAS). Coagulase-positive bacteria nation of Staphylococcus. This is demonstrated by causing mastitis in NAS cows in cows belong to NAS the results of the study by Wanecka A. et al. (2019) are S. agnesi, S. hyicus. One of the studies present- where the genetic material was sequenced the dnaJ ed the prevalence of S. hyicus less than 6.5% . and rpoB genes. This method allowed for the correct Diagnosing the staphylococcus species with NAS is identification of all species . Sequencing meth- much more difficult compared to diagnosing S. au- ods used to mark the genes of the microbes caus- reus. This is due to the multitude of variants and ing mastitis are: ribotyping , pulsed-field gel variability of this group of bacteria, and also due to electrophoresis (PFGE) , multilocus sequence a much more detailed understanding of S. aurues typing (MLST) , amplified fragment length poly- by researchers. Reliability of the examination of morphism (AFLP) , random amplified polymor - the diagnosis of coagulase-positive staphylococcus phic DNA (RAPD) . species other than S. aureus gives the analysis of The occurrence of infections with coagulase-pos- isolates using the MALDI-TOF MS technique (Ma- itive staphylococci is not only dangerous to the trix-assisted laser desorption / ionization time-of- health and life of cows, but also to consumers, due flight mass spectrometry) consisting in pulsed laser to the possibility of accumulating enterotoxins in irradiation of a properly prepared research material milk . The genes responsible for secreting en- and then ionization by being protonated or depro- terotoxins are also detected with different frequen- tonated. The analyzed spectrum gives a high proba- cy. The Fursov study carried out in Russia showed bility to determine the species and their proteins in that the most common gene from the enterotoxino- a short time . Typing a staphylococcal species genic panel was seg (70%). The group of the most on the basis of its phenotype is a much less accurate frequent also includes the gen sea (53.3%) see method. One of the studies reported results where (46.6%) i sec (50%), while the gene sed (4%) was 52 out of 131 (40%) isolates were correctly iden- rare . In another study, the presence of the gene tified (according to the results of the MALDI-TOF sea (35.29%) was at a lower level. The sec gene was MS method). An interesting observation was the much less frequent (5.88%) and there was little fact that 48% of the tested samples were not iden- change in the prevalence of the see gene (47.07%). tified when examining the phenotype . This is Instead, the prevalence of the sed gene changed due to the greater phenotypic lability of staphylo- significantly (29.41%) . In the treatment of cocci . Due to the metabolic properties of the mastitis, intramammary antibiotic therapy is often coagulase positive staphylococcal bacterial cell, it selected [31, 32]. However, the presented data on is possible to judge whether the inflammation is antibiotic resistance and the processes of acquiring staphylococcal because coagulase is a rare enzyme. resistance in bacterial cells necessitates the search This is important because a significant percentage for alternative methods of mastitis treatment. One of inflammation in the mammary gland is caused of the studies compared the effectiveness of antibi- by coagulase-positive staphylococci. However, some otic therapy and non-antibiotic therapy in the treat- studies show the presence of bacterial cells of coag- ment of clinical mastitis . The medicinal product ulase-positive staphylococci species that are unable was supplied as an intramammary syringe contain- to produce coagulase. Such a species is e.g. Staph- ing 120 mg α-tocopherol acetate, 58.83 mg retinol ylococcus hyicus - this bacterium is called coagu- palmitate, 2,400 FIP-U chymotrypsin, 240 FIP-U lase-variable. There are also reports of coagulase trypsin and 6 FIP-U papain. This study compared variability of Staphylococcus aureus . In this the probability of the mastitis coming back 60 days study Saeed Shahmohammadi (2019) presented after healing. In the group treated with antibiotics 200 isolates of Staphylocuccus aureus of which 143 alone, this rate was 53.6%, while the probability of 103 Grzeczka et al. Medical Journal of Cell Biology (2021) 7. Monistero V, Barberio A, Biscarini F, Cremonesi P, Castiglioni B, Graber inflammation recurrence in the group of cows treat- HU, Bottini E, Ceballos-Marquez A, Kroemker V, Petzer IM, Pollera C, ed with the non-antibiotic preparation was 52.2%. 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Advances in Cell Biology – de Gruyter
Published: Sep 1, 2021
Keywords: mastitis; cows; diagnosis; Staphylococcus aureus; coagulase-positive