Half a century of stable antibiotic resistance in livestock-associated Staphylococcus aureus and its dynamic readaptation to humans

Mobile genetic elements (MGEs) often carry genes that benefit their bacterial hosts. In methicillin-resistant Staphylococcus aureus (MRSA), MGEs have been associated with antibiotic resistance, virulence, and host adaptation. Clonal-complex (CC) 398 is the dominant MRSA in European livestock, and a growing cause of human infections. To understand the risk posed by livestock-associated MRSA to human health, we have used a collection of 1,180 CC398 genomes, sampled from several livestock species and humans, with a broad geographic distribution and spanning 27 years, to reconstruct the dynamics of the MGEs. We find that the emergence of livestock-associated CC398 coincided with the acquisition of a Tn916 transposon carrying a tetracycline resistance gene, which has been stably vertically inherited for 57 years. This was followed by the acquisition of a large SCCmec type V element that carries methicillin, tetracycline and heavy metal resistance genes. This has been maintained within livestock-associated CC398 for at least 35 years, with occasional truncations and replacements with other, smaller type IV SCCmec elements. In contrast, a class of prophages that carry a human immune-evasion gene cluster, that are largely absent from livestock-associated CC398, have been repeatedly gained and lost across both human- and livestock-associated CC398. The variable dynamics of these three MGEs means that when livestock-associated MRSA infects humans, re-adaptation to the human host outpaces the loss of antibiotic resistance. Moreover, the stability of both Tn916 and SCCmec suggests that they may persist despite ongoing reductions in antibiotic and zinc oxide use in farming.

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Prevalence and Characterization of Methicillin-Resistant Staphylococcus aureus from Community- and Hospital-Associated Infections: A Tertiary Care Center Study

Antibiotics ◽

10.3390/antibiotics10020197 ◽

2021 ◽

Vol 10 (2) ◽

pp. 197

Author(s):

Puthiya Purayil Preeja ◽

Sanath H. Kumar ◽

Veena Shetty

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Sccmec Type ◽

Tertiary Care ◽

Diffusion Method ◽

Methicillin Resistant ◽

Type Iv ◽

Type V ◽

Hospital Associated Infections

The community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become increasingly prevalent in both community and hospital settings. The aim of this study was to determine the prevalence, molecular characteristics and antibiotic resistance profiles of CA-MRSA from community- and hospital-associated infections in a tertiary care hospital in Mangalore, India. Of 520 S. aureus isolates, 362 were from inpatients (IP) and 158 were from outpatients (OP). One-hundred and thirty-two MRSA isolates obtained from 94 inpatients and 38 outpatients with complete clinical details were further analyzed. Of these, 81 (61.4%) were CA-MRSA (IP-47.9%, OP-94.7%) and 51 (38.6%) were HA-MRSA (IP-52.1%, OP-5.3%). All (100%) MRSA isolates were mecA gene positive. SCCmec typing identified SCCmec type IV (50.6%) and SCCmec type V (66.7%) in CA-MRSA, while SCCmec type I (41.2%), SCCmec type III (19.6%), SCCmec type IV (31.4%) and SCCmec type V (25.5%) were detected in HA-MRSA isolates. The Panton–Valentine Leukocidin (PVL) gene was found in 70.4% of CA-MRSA, 43.1% of HA-MRSA with SCCmec type IV and SCCmec type V, and in 7.8% of true HA-MRSA. The antibiotic resistance profiles were determined by the disc diffusion method. Resistance to cefoxitin was used to identify MRSA. A significant difference (p < 0.05) was observed between CA-MRSA and HA-MRSA with respect to resistance against cephalexin, cefotaxime, levofloxacin, linezolid and teicoplanin. CA-MRSA was predominantly resistant to ciprofloxacin (86.4%), erythromycin (66.7%), ofloxacin (49.4%), cefotaxime (44.4%), gentamicin (40.7%) and clindamycin (40.7%), while HA-MRSA showed resistance against ciprofloxacin (80.4%), erythromycin (80.1%), cefotaxime (70.6%),ofloxacin (58.8%), clindamycin (47.1%) and levofloxacin (41.2%).This study reports the prevalence of CA-MRSA in community and hospital settings and the possibility of multidrug-resistant CA-MRSA replacing HA-MRSA in hospitals. The observations from our study emphasize the need for urgent measures to manage this emerging crisis in healthcare settings.

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Virulence Factors Found in Nasal Colonization and Infection of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates and Their Ability to Form a Biofilm

Toxins ◽

10.3390/toxins13010014 ◽

2020 ◽

Vol 13 (1) ◽

pp. 14

Author(s):

Thamiris Santana Machado ◽

Felipe Ramos Pinheiro ◽

Lialyz Soares Pereira Andre ◽

Renata Freire Alves Pereira ◽

Reginaldo Fernandes Correa ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Methicillin Resistant Staphylococcus Aureus ◽

Sccmec Type ◽

Protein A ◽

Invasive Infection ◽

Type I ◽

Methicillin Resistant ◽

Type Iv ◽

Spa Gene ◽

The City

Hospitalizations related to Methicillin-resistant Staphylococcus aureus (MRSA) are frequent, increasing mortality and health costs. In this way, this study aimed to compare the genotypic and phenotypic characteristics of MRSA isolates that colonize and infect patients seen at two hospitals in the city of Niterói—Rio de Janeiro, Brazil. A total of 147 samples collected between March 2013 and December 2015 were phenotyped and genotyped to identify the protein A (SPA) gene, the mec staphylococcal chromosomal cassette (SCCmec), mecA, Panton-Valentine Leucocidin (PVL), icaC, icaR, ACME, and hla virulence genes. The strength of biofilm formation has also been exploited. The prevalence of SCCmec type IV (77.1%) was observed in the colonization group; however, in the invasive infection group, SCCmec type II was prevalent (62.9%). The Multilocus Sequence Typing (MLST), ST5/ST30, and ST5/ST239 analyses were the most frequent clones in colonization, and invasive infection isolates, respectively. Among the isolates selected to assess the ability to form a biofilm, 51.06% were classified as strong biofilm builders. Surprisingly, we observed that isolates other than the Brazilian Epidemic Clone (BEC) have appeared in Brazilian hospitals. The virulence profile has changed among these isolates since the ACME type I and II genes were also identified in this collection.

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Distribution of virulence genes and SCCmec types among methicillin-resistant Staphylococcus aureus of clinical and environmental origin: a study from community of Assam, India

BMC Research Notes ◽

10.1186/s13104-021-05473-3 ◽

2021 ◽

Vol 14 (1) ◽

Cited By ~ 1

Author(s):

Deepshikha Bhowmik ◽

Shiela Chetri ◽

Bhaskar Jyoti Das ◽

Debadatta Dhar Chanda ◽

Amitabha Bhattacharjee

Keyword(s):

Staphylococcus Aureus ◽

Virulence Genes ◽

Methicillin Resistant Staphylococcus Aureus ◽

Virulence Gene ◽

Type I ◽

Methicillin Resistant ◽

Type Iv ◽

Clinical Community ◽

Type V ◽

Sccmec Types

Abstract Objective This study was designed to discover the dissemination of virulence genes in Methicillin-resistant Staphylococcus aureus from clinical, community and environmental settings. Results This study includes 1165 isolates collected from hospital, community and environmental settings. Among them sixty three were confirmed as MRSA with varied SCCmec types viz; type I, type II, type III, type IV, type V, type VI, type VII, type VIII and type XII. The virulence gene such as sea (n = 54), seb (n = 21), eta (n = 27), etb (n = 2), cna (n = 24), ica (n = 2) and tst (n = 30) was also revealed from this study. The study underscores coexistence of resistance cassette and virulence genes among clinical and environment isolates which is first of its kind from this part of the world.

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The First Report of a Methicillin-Resistant Staphylococcus aureus Isolate Harboring Type IV SCCmec in Thailand

Pathogens ◽

10.3390/pathogens10040430 ◽

2021 ◽

Vol 10 (4) ◽

pp. 430

Author(s):

Wichai Santimaleeworagun ◽

Praewdow Preechachuawong ◽

Wandee Samret ◽

Tossawan Jitwasinkul

Keyword(s):

Staphylococcus Aureus ◽

Resistance Genes ◽

Methicillin Resistant Staphylococcus Aureus ◽

Methicillin Resistance ◽

Sccmec Type ◽

Clinical Strain ◽

Spa Typing ◽

Methicillin Resistant ◽

Type Iv ◽

Antimicrobial Resistance Genes

Methicillin-resistant Staphylococcus aureus (MRSA) is mostly found in Thailand in the hospital as a nosocomial pathogen. This study aimed to report the genetic characterization of a clinical community-acquired MRSA (CA-MRSA) isolate collected from hospitalized patients in Thailand. Among 26 MRSA isolates, S. aureus no. S17 preliminarily displayed the presence of a staphylococcal cassette chromosome mec (SCCmec) type IV pattern. The bacterial genomic DNA was subjected to whole-genome sequencing. Panton–Valentine leukocidin (PVL) production, virulence toxins, and antibiotic resistance genes were identified, and multi-locus sequence typing (MLST) and spa typing were performed. The strain was matched by sequence to MLST type 2885 and spa type t13880. This strain carried type IV SCCmec with no PVL production. Five acquired antimicrobial resistance genes, namely blaZ, mecA, Inu(A), tet(K), and dfrG conferring resistance to β-lactams, lincosamides, tetracycline, and trimethoprim, were identified. The detected toxins were exfoliative toxin A, gamma-hemolysin, leukocidin D, and leukocidin E. Moreover, there were differences in seven regions in CR-MRSA no. S17 compared to CA-MRSA type 300. In summary, we have reported the ST2885-SCCmec IV CA-MRSA clinical strain in Thailand for the first time, highlighting the problem of methicillin resistance in community settings and the consideration in choosing appropriate antibiotic therapy.

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ε2-Phages Are Naturally Bred and Have a Vastly Improved Host Range in Staphylococcus aureus over Wild Type Phages

Pharmaceuticals ◽

10.3390/ph14040325 ◽

2021 ◽

Vol 14 (4) ◽

pp. 325

Author(s):

David Sáez Moreno ◽

Zehra Visram ◽

Michele Mutti ◽

Marcela Restrepo-Córdoba ◽

Susana Hartmann ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Detection Limit ◽

Host Range ◽

Alternative Treatment ◽

Standard Of Care ◽

Wild Type ◽

Rapid Spread ◽

Pharmaceutical Properties ◽

Human Infections

Due to the rapid spread of antibiotic resistance, and the difficulties of treating biofilm-associated infections, alternative treatments for S. aureus infections are urgently needed. We tested the lytic activity of several wild type phages against a panel of 110 S. aureus strains (MRSA/MSSA) composed to reflect the prevalence of S. aureus clonal complexes in human infections. The plaquing host ranges (PHR) of the wild type phages were in the range of 51% to 60%. We also measured what we called the kinetic host range (KHR), i.e., the percentage of strains for which growth in suspension was suppressed for 24 h. The KHR of the wild type phages ranged from 2% to 49%, substantially lower than the PHRs. To improve the KHR and other key pharmaceutical properties, we bred the phages by mixing and propagating cocktails on a subset of S. aureus strains. These bred phages, which we termed evolution-squared (ε2) phages, have broader KHRs up to 64% and increased virulence compared to the ancestors. The ε2-phages with the broadest KHR have genomes intercrossed from up to three different ancestors. We composed a cocktail of three ε2-phages with an overall KHR of 92% and PHR of 96% on 110 S. aureus strains and called it PM-399. PM-399 has a lower propensity to resistance formation than the standard of care antibiotics vancomycin, rifampicin, or their combination, and no resistance was observed in laboratory settings (detection limit: 1 cell in 1011). In summary, ε2-phages and, in particular PM-399, are promising candidates for an alternative treatment of S. aureus infections.

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Staphylococcus aureus Infections in Malaysia: A Review of Antimicrobial Resistance and Characteristics of the Clinical Isolates, 1990–2017

Antibiotics ◽

10.3390/antibiotics8030128 ◽

2019 ◽

Vol 8 (3) ◽

pp. 128 ◽

Cited By ~ 3

Author(s):

Ainal Mardziah Che Hamzah ◽

Chew Chieng Yeo ◽

Suat Moi Puah ◽

Kek Heng Chua ◽

Ching Hoong Chew

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Resistance ◽

Sccmec Type ◽

Epidemiological Data ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Type Iv ◽

Resistant Strains ◽

Vancomycin Resistant ◽

Comprehensive Surveillance

Staphylococcus aureus is an important nosocomial pathogen and its multidrug resistant strains, particularly methicillin-resistant S. aureus (MRSA), poses a serious threat to public health due to its limited therapeutic options. The increasing MRSA resistance towards vancomycin, which is the current drug of last resort, gives a great challenge to the treatment and management of MRSA infections. While vancomycin resistance among Malaysian MRSA isolates has yet to be documented, a case of vancomycin resistant S. aureus has been reported in our neighboring country, Indonesia. In this review, we present the antimicrobial resistance profiles of S. aureus clinical isolates in Malaysia with data obtained from the Malaysian National Surveillance on Antimicrobial Resistance (NSAR) reports as well as various peer-reviewed published records spanning a period of nearly three decades (1990–2017). We also review the clonal types and characteristics of Malaysian S. aureus isolates, where hospital-associated (HA) MRSA isolates tend to carry staphylococcal cassette chromosome mec (SCCmec) type III and were of sequence type (ST)239, whereas community-associated (CA) isolates are mostly SCCmec type IV/V and ST30. More comprehensive surveillance data that include molecular epidemiological data would enable further in-depth understanding of Malaysian S. aureus isolates.

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Distribution of Virulence Genes Among Methicillin-resistant Staphylococcus Aureus of Clinical and Environmental Origin

10.21203/rs.3.rs-87157/v1 ◽

2020 ◽

Author(s):

Deepshikha Bhowmik ◽

Shiela Chetri ◽

Bhaskar Jyoti Das ◽

Debadatta Dhar Chanda ◽

Amitabha Bhattacharjee

Keyword(s):

Staphylococcus Aureus ◽

Multidrug Resistance ◽

Virulence Genes ◽

Methicillin Resistant Staphylococcus Aureus ◽

Virulence Gene ◽

Type I ◽

Type Ii ◽

Methicillin Resistant ◽

Type Iv ◽

Type V

Abstract Objective: This study was designed to discover the dissemination of virulence genes in Methicillin-resistant Staphylococcus aureus from clinical and environmental settings. Results: The virulence gene such as sea (n=54), seb (n=21), eta (n=27), etb (n=2), cna (n=24), ica (n=2) and tst (n=30) was revealed from this study. Different SCCmec types such as type I, type II, type III, type IV, type V, type VI, type VII, type VIII and type XII were detected among sixty three MRSA isolates where SCCmec type II having ST1551 and type V with ST2416 were found to be associated with multidrug resistance and were highly prevalent in the study area.

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Comparison of Methicillin-Resistant Staphylococcus aureus Isolates from Cellulitis and from Osteomyelitis in a Taiwan Hospital, 2016–2018

Journal of Clinical Medicine ◽

10.3390/jcm8060816 ◽

2019 ◽

Vol 8 (6) ◽

pp. 816 ◽

Cited By ~ 1

Author(s):

Kuo-Ti Peng ◽

Tsung-Yu Huang ◽

Yao-Chang Chiang ◽

Yu-Yi Hsu ◽

Fang-Yi Chuang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Methicillin Resistant Staphylococcus Aureus ◽

Joint Infection ◽

Sccmec Type ◽

Multidrug Resistant ◽

Chang Gung Memorial Hospital ◽

Methicillin Resistant ◽

Mrsa Strains ◽

Resistance Rates

Methicillin-resistant Staphylococcus aureus (MRSA) causes superficial infections such as cellulitis or invasive infections such as osteomyelitis; however, differences in MRSA isolates from cellulitis (CL-MRSA) and from osteomyelitis (OM-MRSA) at the same local area remain largely unknown. A total of 221 MRSA isolates including 106 CL-MRSA strains and 115 OM-MRSA strains were collected at Chang-Gung Memorial Hospital in Taiwan between 2016 and 2018, and their genotypic and phenotypic characteristics were compared. We found that OM-MRSA isolates significantly exhibited higher rates of resistance to multiple antibiotics than CL-MRSA isolates. Genotypically, OM-MRSA isolates had higher proportions of the SCCmec type III, the sequence type ST239, and the spa type t037 than CL-MRSA isolates. Besides the multidrug-resistant lineage ST239-t037-SCCmecIII more prevalent in OM-MRSA, higher antibiotic resistance rates were also observed in several other prevalent lineages in OM-MRSA as compared to the same lineages in CL-MRSA. Furthermore, when prosthetic joint infection (PJI) associated and non-PJI-associated MRSA strains in osteomyelitis were compared, no significant differences were observed in antibiotic resistance rates between the two groups, albeit more diverse genotypes were found in non-PJI-associated MRSA. Our findings therefore suggest that deep infections may allow MRSA to evade antibiotic attack and facilitate the convergent evolution and selection of multidrug-resistant lineages.

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