Evidence for a Clonal Origin of Methicillin Resistance in Staphylococcus aureus
08 Jan 1993-Science (American Association for the Advancement of Science)-Vol. 259, Iss: 5092, pp 227-230
TL;DR: An investigation of the clonality of 472 isolates by DNA hybridization was performed, suggesting that mecA divergence preceded the acquisition of Tn554 in all cases and therefore thatmecA may have been acquired just once by S. aureus.
Abstract: Soon after methicillin was introduced into clinical practice in the early 1960s, resistant strains of Staphylococcus aureus (MRSA) appeared, bearing a newly acquired resistance gene, mecA, that encodes a penicillin binding protein, PBP2a. MRSA have spread throughout the world, and an investigation of the clonality of 472 isolates by DNA hybridization was performed. All 472 isolates could be divided into six temporally ordered mecA hybridization patterns, and three of these were subdivided by the chromomosomal transposon Tn554. Each Tn554 pattern occurred in association with one and only one mecA pattern, suggesting that mecA divergence preceded the acquisition of Tn554 in all cases and therefore that mecA may have been acquired just once by S. aureus.
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TL;DR: This research presents a novel, scalable and scalable approach that allows for real-time assessment of the severity of the infection and its impact on patients’ health.
Abstract: FRED C. TENOVER,* ROBERT D. ARBEIT, RICHARD V. GOERING, PATRICIA A. MICKELSEN, BARBARA E. MURRAY, DAVID H. PERSING, AND BALA SWAMINATHAN National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333; Veterans Affairs Medical Center, Boston, Massachusetts 02130; Creighton University, Omaha, Nebraska 68178; Stanford University Medical Center, Stanford, California 94305; University of Texas Medical School, Houston, Texas 77030; and Mayo Clinic, Rochester, Minnesota 55905
7,784 citations
Cites background from "Evidence for a Clonal Origin of Met..."
...aureus are derived from a small number of ancestral clones (24, 36, 44)....
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TL;DR: In an elegant series of clinical observations and laboratory studies published in 1880 and 1882, Ogston described staphylococcal disease and its role in sepsis and abscess formation.
Abstract: Micrococcus, which, when limited in its extent and activity, causes acute suppurative inflammation (phlegmon), produces, when more extensive and intense in its action on the human system, the most virulent forms of septicaemia and pyaemia.1 In an elegant series of clinical observations and laboratory studies published in 1880 and 1882, Ogston described staphylococcal disease and its role in sepsis and abscess formation.1,2 More than 100 years later, Staphylococcus aureus remains a versatile and dangerous pathogen in humans. The frequencies of both community-acquired and hospital-acquired staphylococcal infections have increased steadily, with little change in overall mortality. Treatment of these infections . . .
5,550 citations
TL;DR: It is suggested that most community-associated MRSA strains did not originate in health care settings, and that their microbiological features may have contributed to their emergence in the community.
Abstract: Context Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been considered a health care–associated pathogen in patients with established risk factors. However, MRSA has emerged in patients without established risk factors (community-associated MRSA). Objective To characterize epidemiological and microbiological characteristics of community-associated MRSA cases compared with health care–associated MRSA cases. Design, Setting, and Patients Prospective cohort study of patients with MRSA infection identified at 12 Minnesota laboratory facilities from January 1 through December 31, 2000, comparing community-associated (median age, 23 years) with health care–associated (median age, 68 years) MRSA cases. Main Outcome Measures Clinical infections associated with either communityassociated or health care–associated MRSA, microbiological characteristics of the MRSA isolates including susceptibility testing, pulsed-field gel electrophoresis, and staphylococcal exotoxin gene testing. Results Of 1100 MRSA infections, 131 (12%) were community-associated and 937 (85%) were health care–associated; 32 (3%) could not be classified due to lack of information. Skin and soft tissue infections were more common among communityassociated cases (75%) than among health care–associated cases (37%) (odds ratio [OR], 4.25; 95% confidence interval [CI], 2.97-5.90). Although communityassociated MRSA isolates were more likely to be susceptible to 4 antimicrobial classes (adjusted OR, 2.44; 95% CI, 1.35-3.86), most community-associated infections were initially treated with antimicrobials to which the isolate was nonsusceptible. Communityassociated isolates were also more likely to belong to 1 of 2 pulsed-field gel electrophoresis clonal groups in both univariate and multivariate analysis. Communityassociated isolates typically possessed different exotoxin gene profiles (eg, Panton Valentine leukocidin genes) compared with health care–associated isolates. Conclusions Community-associated and health care–associated MRSA cases differ demographically and clinically, and their respective isolates are microbiologically distinct. This suggests that most community-associated MRSA strains did not originate in health care settings, and that their microbiological features may have contributed to their emergence in the community. Clinicians should be aware that therapy with -lactam antimicrobials can no longer be relied on as the sole empiric therapy for severely ill outpatients whose infections may be staphylococcal in origin.
1,779 citations
TL;DR: This work analyzes an international collection of 912 MRSA and methicillin-susceptible S. aureus isolates to establish the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSAclone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methiillin resistance genes.
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. The evolutionary origins of MRSA are poorly understood, no rational nomenclature exists, and there is no consensus on the number of major MRSA clones or the relatedness of clones described from different countries. We resolve all of these issues and provide a more thorough and precise analysis of the evolution of MRSA clones than has previously been possible. Using multilocus sequence typing and an algorithm, burst, we analyzed an international collection of 912 MRSA and methicillin-susceptible S. aureus (MSSA) isolates. We identified 11 major MRSA clones within five groups of related genotypes. The putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor were inferred by using burst, which, together with analysis of the methicillin resistance genes, established the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSA clone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methicillin resistance genes. Major MRSA clones have arisen repeatedly from successful epidemic MSSA strains, and isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes.
1,653 citations
TL;DR: Strains of methicillin-resistant Staphylococcus aureus, which had been largely confined to hospitals and long-term care facilities, are emerging in the community, and the prevalence of these strains in thecommunity seems likely to increase substantially.
Abstract: Strains of methicillin-resistant Staphylococcus aureus (MRSA), which had been largely confined to hospitals and long-term care facilities, are emerging in the community. The changing epidemiology of MRSA bears striking similarity to the emergence of penicillinase-mediated resistance in S. aureus decades ago. Even though the origin (hospital or the community) of the emerging MRSA strains is not known, the prevalence of these strains in the community seems likely to increase substantially.
1,577 citations
Cites background from "Evidence for a Clonal Origin of Met..."
...Horizontal transfer of mec is thought to be relatively rare; only a handful of ancestral strains account for all clinical isolates worldwide (25)....
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References
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TL;DR: The results indicate that M. tuberculosis strains from regions in central Africa, where tuberculosis is highly prevalent, are generally more related to each other than isolates from the Netherlands, where the transmission rate is low and where the majority of the tuberculosis cases are presumed to be the result of reactivation of previously contracted M.culosis infections.
Abstract: In this study we established the usefulness of DNA fingerprinting for the epidemiology of tuberculosis on the basis of the DNA polymorphism generated by the insertion sequence (IS) IS986. Although clinical isolates of Mycobacterium tuberculosis displayed a remarkably high degree of restriction fragment length polymorphism, we showed that transposition of this IS element is an extremely rare event in M. tuberculosis complex strains grown either in vitro or in vivo for long periods of time. The M. tuberculosis and Mycobacterium africanum strains tested in this study contained 6 to 17 IS copies. In the Mycobacterium bovis strains, the copy numbers ranged between 1 and 5, and all 27 M. bovis BCG strains investigated invariably contained a single IS copy. This copy was located at a unique chromosomal position, reinforcing the idea that the frequency of IS transposition is very low in M. tuberculosis complex strains. Various microepidemics are described in which each microepidemic corresponds to a particular fingerprint type. The extent of similarity between Dutch and African strains was quantitatively assessed by computer-assisted analysis of DNA fingerprints. The results indicate that M. tuberculosis strains from regions in central Africa, where tuberculosis is highly prevalent, are generally more related to each other than isolates from the Netherlands, where the transmission rate is low and where the majority of the tuberculosis cases are presumed to be the result of reactivation of previously contracted M. tuberculosis infections.
989 citations
TL;DR: Using techniques of molecular epidemiology, the authors demonstrate that an organism isolated from the vitreous was genetically indistinguishable from an isolate recovered from the patient's eyelid, conjunctiva, or nose in 14 (82%) of 17 cases of endophthalmitis.
618 citations
Book•
30 Nov 1990
TL;DR: Introduction genome organization and evolution gene transfer and transposons plasmids exoproteins and pathogenicity factors resistance and its spread resistance and epidemiology.
Abstract: Introduction genome organization and evolution gene transfer and transposons plasmids exoproteins and pathogenicity factors resistance and its spread resistance and epidemiology.
272 citations
TL;DR: There is geographic variation in the frequency of recovery of the common methicillin-resistant clones, an observation that may in part explain reported regional differences in natural history correlates of resistant organisms.
Abstract: Genetic relationships among 254 isolates of Staphylococcus aureus resistant to methicillin recovered between 1961 and 1992 from nine countries on four continents were determined by analyzing electrophoretically demonstrable allelic variation at 15 chromosomal enzyme loci. Fifteen distinctive electrophoretic types, marking clones, were identified. The mec gene is harbored by many divergent phylogenetic lineages representing a large portion of the breadth of chromosomal diversity in the species, a result that is interpreted as evidence that multiple episodes of horizontal transfer and recombination have contributed to the spread of this resistance determinant in natural populations. Isolates recovered in the United Kingdom, Denmark, Switzerland, Egypt, and Uganda in the 1960s are of a single multilocus enzyme genotype and probably are progeny of an ancestral methicillin-resistant clone. There is geographic variation in the frequency of recovery of the common methicillin-resistant clones, an observation that may in part explain reported regional differences in natural history correlates of resistant organisms.
239 citations