Even though antibiotic resistance in bacteria is a natural phenomenon, the alarming increase in pathogenic bacteria refractory to a wide range of antimicrobials is attracting attention worldwide. ...Indeed, the World Health Organization (WHO) has recently published a list of priority pathogens for which new antimicrobial alternatives are urgently needed. Among these pathogens, methicillin-resistant
(MRSA) strains are perhaps the best known by the general public. In addition to its potential to acquire antibiotic resistance,
can produce a large number of virulence factors, such as hemolysins, enterotoxins, and proteases, and exhibits the ability to form biofilms as well as to evolve into different clones that can spread and colonize new environments. This review provides a brief overview of the latest options in antibacterial therapies, mainly focusing on phage therapy. In this regard, the current stage of research about antimicrobial compounds based on bacteriophages and endolysins against MRSA infections is shown and discussed.
Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) isolates (n = 178) collected in the national resistance monitoring program GERM-Vet from diseased ...swine in Germany from 2007 to 2019 were investigated for their genomic diversity with a focus on virulence and antimicrobial resistance (AMR) traits. Whole-genome sequencing was followed by molecular typing and sequence analysis. A minimum spanning tree based on core-genome multilocus sequence typing was constructed, and antimicrobial susceptibility testing was performed. Most isolates were assigned to nine clusters. They displayed close phylogenetic relationships but a wide molecular variety, including 13 spa types and 19 known and four novel dru types. Several toxin-encoding genes, including eta, seb, sek, sep, and seq, were detected. The isolates harbored a wide range of AMR properties mirroring the proportions of the classes of antimicrobial agents applied in veterinary medicine in Germany. Multiple novel or rare AMR genes were identified, including the phenicol-lincosamide-oxazolidinone-pleuromutilin-streptogramin A resistance gene cfr, the lincosamide-pleuromutilin-streptogramin A resistance gene vga(C), and the novel macrolide-lincosamide-streptogramin B resistance gene erm(54). Many AMR genes were part of small transposons or plasmids. Clonal and geographical correlations of molecular characteristics and resistance and virulence genes were more frequently observed than temporal relations. In conclusion, this study provides insight into population dynamics of the main epidemic porcine LA-MRSA lineage in Germany over a 13-year-period. The observed comprehensive AMR and virulence properties, most likely resulting from the exchange of genetic material between bacteria, highlighted the importance of LA-MRSA surveillance to prevent further dissemination among swine husbandry facilities and entry into the human community. IMPORTANCE The LA-MRSA-CC398 lineage is known for its low host specificity and frequent multiresistance to antimicrobial agents. Colonized swine and their related surroundings represent a considerable risk of LA-MRSA-CC398 colonization or infection for occupationally exposed people through which such isolates might be further disseminated within the human community. This study provides insight into the diversity of the porcine LA-MRSA-CC398 lineage in Germany. Clonal and geographical correlations of molecular characteristics and resistance and virulence traits were detected and may be associated with the spread of specific isolates through livestock trade, human occupational exposure, or dust emission. The demonstrated genetic variability underlines the lineage’s ability to horizontally acquire foreign genetic material. Thus, LA-MRSA-CC398 isolates have the potential to become even more dangerous for various host species, including humans, due to increased virulence and/or limited therapeutic options for infection control. Full-scale LA-MRSA monitoring at the farm, community, and hospital level is therefore essential.
Livestock-associated (LA)-CC398-MRSA is closely related to pigs, being unfrequently detected in human invasive infections. CC398-MSSA is emerging in human invasive infections in some countries, but ...genetic and epidemiological characteristics are still scarcely reported.
To determine the prevalence of
(SA) CC398, both MRSA and MSSA, among blood cultures SA isolates recovered in Spanish hospitals located in regions with different pig-farming densities (PD) and characterize the recovered isolates.
One thousand twenty-two SA isolates (761 MSSA, 261 MRSA) recovered from blood cultures during 6-12 months in 17 Spanish hospitals (2018-2019) were studied. CC398 lineage identification, detection of
-types, and antibiotic resistance, virulence and human immune evasion cluster (IEC) genes were analyzed by PCR/sequencing.
Forty-four CC398-MSSA isolates (4.3% of SA; 5.8% of MSSA) and 10 CC398-MRSA isolates (1% of SA; 3.8% of MRSA) were detected. Eleven
-types were found among the CC398-MSSA isolates with t571 and t1451 the most frequent
-types detected (75%). Most of CC398-MSSA isolates were Immune-Evasion-Cluster (IEC)-positive (88.6%), tetracycline-susceptible (95.5%) and erythromycin/clindamycin
-resistant/
(T)-positive (75%). No statistical significance was detected when the CC398-MSSA/MSSA rate was correlated to PD (pigs/km
) (
= 0.108). On the contrary, CC398-MRSA isolates were all IEC-negative, predominately
-t011 (70%), and the CC398-MRSA/MRSA rate was significantly associated to PD (
< 0.005).
CC398-MSSA is an emerging clade in invasive infections in Spanish hospitals. CC398-MRSA (mostly t011) and CC398-MSSA (mostly t571 and t1451) show important differences, possibly suggesting divergent steps in host-adaptation evolutionary processes. While CC398-MRSA is livestock-associated (lacking IEC-system), CC398-MSSA seems to be mostly livestock-independent, carrying human-adaptation markers.
This paper discusses the mechanisms of S. aureus drug resistance including: (1) introduction. (2) resistance to beta-lactam antibiotics, with particular emphasis on the mec genes found in the ...Staphylococcaceae family, the structure and occurrence of SCCmec cassettes, as well as differences in the presence of some virulence genes and its expression in major epidemiological types and clones of HA-MRSA, CA-MRSA, and LA-MRSA strains. Other mechanisms of resistance to beta-lactam antibiotics will also be discussed, such as mutations in the gdpP gene, BORSA or MODSA phenotypes, as well as resistance to ceftobiprole and ceftaroline. (3) Resistance to glycopeptides (VRSA, VISA, hVISA strains, vancomycin tolerance). (4) Resistance to oxazolidinones (mutational and enzymatic resistance to linezolid). (5) Resistance to MLS-B (macrolides, lincosamides, ketolides, and streptogramin B). (6) Aminoglycosides and spectinomicin, including resistance genes, their regulation and localization (plasmids, transposons, class I integrons, SCCmec), and types and spectrum of enzymes that inactivate aminoglycosides. (7). Fluoroquinolones (8) Tetracyclines, including the mechanisms of active protection of the drug target site and active efflux of the drug from the bacterial cell. (9) Mupirocin. (10) Fusidic acid. (11) Daptomycin. (12) Resistance to other antibiotics and chemioterapeutics (e.g., streptogramins A, quinupristin/dalfopristin, chloramphenicol, rifampicin, fosfomycin, trimethoprim) (13) Molecular epidemiology of MRSA.
Methicillin-resistant Staphylococcus aureus (MRSA) can be transmitted between pigs and humans on farms. Hence, the reduction of MRSA carriage in pigs could decrease the risk of zoonotic transmission. ...Recently, straw bedding has been found to significantly reduce MRSA carriage in pigs. The mechanisms behind this effect remain unclear but changes in the nasal microbiome may play a role. In this exploratory study, the nasal microbiota of pigs kept on straw was examined using V1/V2 16S rRNA gene sequencing. Nasal swabs were collected from 13 pigs at six different time points during the course of a full fattening cycle resulting in 74 porcine samples. In addition, straw samples were collected at each time point. Eleven out of 13 pigs were MRSA positive at housing-in. We found a strong temporal pattern in the microbial communities. Both microbial diversity and abundance of Staphylococcus species peaked in week 5 after introduction to the straw stable decreased in week 10, when all pigs turned MRSA-negative, and increased again toward the end of the fattening period. These findings show that the introduction of pigs into a new environment has a huge impact on their nasal microbiota, which might lead to unfavorable conditions for MRSA. Moreover, other Staphylococcus species may play a role in eliminating MRSA carriage. We designed a follow-up study including two different husbandry systems to further assess these effects.
Infections caused by methicillin-resistant
(MRSA) have been a growing problem in human medicine since the 1960s, and more recently in veterinary medicine with the appearance of livestock-associated ...MRSA (LA-MRSA). Nevertheless, information about the presence of MRSA in rabbits is quite scarce since only one LA-MRSA identification has been previously reported. The present study aimed to determine genotypic characterization by verifying the presence of resistance determinants, virulence, and toxin genes of different
strains that cause lesions in rabbits, and their phenotypic traits based on the antimicrobial susceptibility profile. The analysis of 240
isolates obtained from different lesion types collected from 89 Spanish and Portuguese rabbit commercial farms in the last 4 years (2014-2017) was performed. The methicillin-resistant gene
A was found in 11.25% of the studied isolates (27 of 240) from 19 farms (13 Spanish and 6 Portuguese). Staphylococcal cassette chromosome
(SCC
) typing predominantly revealed type III (
= 15). Additionally, three MRSA isolates carrying the
C gen were detected in samples from three different farms (two Spanish and one Portuguese). None of the 30 MRSA isolates was
-positive or
-positive. After the multilocus sequence typing (MLST) procedure, 16 belonged to ST2855, 6 to ST146, 6 to ST398, and 2 ST4774. No ST121 isolate was
-positive. ST398 and ST4774 isolates lacked the immune-evasion-cluster (IEC) genes. ST2855 strains were associated with the presence only of the
gene, and ST146 isolates were ascribed to IEC type E. Therefore, this is the first description of LA-MRSA from rabbits belonging to ST2855. Interestingly, one ST2855 and two ST4774 isolates were
C-positive, which could act as a
C-MRSA reservoir. More studies are needed to further characterize these isolates and their relationship with humans and other animal species.
Livestock-associated methicillin-resistant
(LA-MRSA) isolates of the clonal complex 398 are often resistant to a number of antimicrobial agents. Studies on the genetic basis of antimicrobial ...resistance in these bacteria identified SCC
cassettes, various transposons and plasmids of different sizes that harbor antimicrobial resistance genes. While large plasmids that carry multiple antimicrobial resistance genes - occasionally together with heavy metal resistance genes and/or virulence genes - are frequently seen in LA-MRSA ST398, certain resistance genes are also associated with small plasmids of up to 15 kb in size. These small resistance plasmids usually carry only one, but in rare cases also two or three antimicrobial resistance genes. In the current review, we focus on small plasmids that carry the macrolide-lincosamide-streptogramin B resistance genes
(C) or
(T), the lincosamide resistance gene
(A), the pleuromutilin-lincosamide-streptogramin A resistance genes
(A) or
(C), the spectinomycin resistance gene
, the apramycin resistance gene
, or the trimethoprim resistance gene
. The detailed analysis of the structure of these plasmids allows comparisons with similar plasmids found in other staphylococci and underlines in many cases an exchange of such plasmids between LA-MRSA ST398 and other staphylococci including also coagulase-negative staphylococci.
Livestock-associated methicillin-resistant
Staphylococcus aureus
(LA-MRSA) is a major concern in many parts of the world, including Pakistan. The aim of this study was to investigate the prevalence ...of MRSA in slaughterhouses and meat shops in Rawalpindi-Islamabad, Pakistan, 2018–2019. A total of 300 samples were collected: 40 from each of working area, tools (knives, hooks), butcher hands and beef, 30 from each of chicken and mutton, 20 from each of nasal and rectal swabs.
S. aureus
was phenotypically identified by performing gram staining and biochemical tests. 150 of the 300 samples were confirmed to be
S. aureus
by phenotypic identification. MRSA was identified among
S. aureus
positive isolates by performing disk diffusion test and by detecting
S. aureus
-specific genes such as 16s rRNA,
nuc
,
mecA
,
spa
, and
coa
. Out of 150 isolates 96 (63%) showed resistance to antibiotic cefoxitin, known as a potential marker for detecting MRSA. While all 150 isolates have shown complete resistance to the four antibiotics neomycin, methicillin, ciprofloxacin and tetracycline. The
nuc
and 16s rRNA genes were detected in all 150
S. aureus-
positive isolates and 118 (79%) were confirmed to be MRSA through the detection of the
mecA
gene. MRSA prevalence was highest in chicken (23/30, 77%) followed by beef (25/40, 63%), mutton (15/30, 50%), knives (18/40, 45%), nasal swabs (7/20, 35%), working area (11/40, 28%), rectal swabs (5/20, 25%), hooks (7/40, 18%), and butcher hands (7/40, 18%). 50 MRSA-positive isolates were chosen to identify two virulence factors (
spa
and
coa
gene). Of the 50 MRSA isolates subject to
coa
and
spa
gene typing, 27 (54%) were positive for the
coa
gene and 18 (36%) were positive for the
spa
gene, respectively. To the best of our knowledge, this was the first study on the molecular identification of MRSA in meat samples from Pakistan. High prevalence of MRSA in meat samples demand for implementation of proper hygienic practices and procedures during the slaughtering, transport and marketing of meat and meat products in order to prevent the spread of these bacteria to the human population.
Farm animals have been identified as an emerging reservoir for transmission of livestock-associated methicillin-resistant
(LA-MRSA) to humans. The low incidence of MRSA in humans and farm animals in ...Norway has led to the implementation of a national strategy of surveillance and control of LA-MRSA aiming to prevent livestock becoming a domestic source of MRSA to humans. In 2015, MRSA clonal complex 1
-type t177 was identified in nine Norwegian pig herds in two neighboring counties. An outbreak investigation was undertaken, and measures of control through eradication were imposed. We performed a register-based cohort study including pig herds and MRSA-positive persons in Norway between 2008 and 2016 to investigate the livestock-association of MRSA CC1, the transmission of the outbreak strain to humans before and after control measures, and the effect of control measures imposed. Data from the Norwegian Surveillance System of Communicable Diseases were merged with data collected through outbreak investigations for LA-MRSA, the National Registry and the Norwegian Register for Health Personnel. Whole-genome sequencing was performed on isolates from livestock and humans identified through contact tracing, in addition to t177 and t127 isolates diagnosed in persons in the same counties. It is likely that a farm worker introduced MRSA CC1 to a sow farm, and further transmission to eight fattening pig farms through trade of live pigs confirmed the potential for livestock association of this MRSA type. The outbreak strain formed a distinct phylogenetic cluster which in addition to the pig farms included one sheep herd and five exposed persons. None of the investigated isolates from possible cases without direct contact to the MRSA positive farms were phylogenetically related to the outbreak strain. Moreover, isolates of t177 or t127 from healthcare and community-acquired cases were not closely related to the outbreak cluster. Eradication measures imposed were effective in eliminating MRSA t177 from the positive pig holdings, and the outbreak strain was not detected in the national pig population or in persons from these counties after control measures.
Livestock-associated
(LA-MRSA) has been of increasing concern due to its potential risk to humans. This study investigated the prevalence of MRSA in pig production in Eastern China and determined the ...genomic characteristics of pig-associated MRSA isolates by whole-genome sequencing (WGS). A total of 1,318 samples were collected from pig farms and pig slaughterhouses, and 150
were identified, including 63 MRSA isolates and 87 MSSA isolates. MRSA was detected in all pig farms and pig slaughterhouses. The antimicrobial susceptibility test revealed that all MRSA isolates were multidrug-resistant. The WGS and MLST analysis demonstrated that 56 MRSA isolates belonged to clonal complex (CC) 398, and seven MRSA isolates belonged to CC9. All LA-MRSA isolates were absent of phiSa3 phage containing immune evasion cluster (IEC) and possessed an intact
gene. In addition, genes associated with Panton-Valentine leukocidin, typically indicative of human adaptation, were not detected. The analysis of antibiotic resistance genes (ARGs) demonstrated that all MRSA isolates contained multiple ARGs. All MRSA isolates had Plthe
gene and at least one tetracycline resistance gene. Both
and
were detected in all MRSA CC398 isolates, while
was detected in all MRSA CC9 isolates. The phenicol resistance gene
was detected in 51 MRSA isolates, while the linezolid resistance gene
was detected in 60 MRSA isolates. The emergence of LA-MRSA CC398 in four pig farms and one slaughterhouse in this study indicates the spread of this clonal complex in the pig production sector in Eastern China. Further investigations are required to understand the potential transmission routes of LA-MRSA CC398 within the pork production chain in China and to assess the potential risks to humans.
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