SCCmec transformation requires living donor cells in mixed biofilms
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ABSTRACT:
SUBMITTER: Maree M
PROVIDER: S-EPMC10909703 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
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Project description:Several lines of evidence indicate that the most primitive staphylococcal species, those of the Staphylococcus sciuri group, were involved in the first stages of evolution of the staphylococcal cassette chromosome mec (SCCmec), the genetic element carrying the β-lactam resistance gene mecA However, many steps are still missing from this evolutionary history. In particular, it is not known how mecA was incorporated into the mobile element SCC prior to dissemination among Staphylococcus aureus and other pathogenic staphylococcal species. To gain insights into the possible contribution of several species of the Staphylococcus sciuri group to the assembly of SCCmec, we sequenced the genomes of 106 isolates, comprising S. sciuri (n = 76), Staphylococcus vitulinus (n = 18), and Staphylococcus fleurettii (n = 12) from animal and human sources, and characterized the native location of mecA and the SCC insertion site by using a variety of comparative genomic approaches. Moreover, we performed a single nucleotide polymorphism (SNP) analysis of the genomes in order to understand SCCmec evolution in relation to phylogeny. We found that each of three species of the S. sciuri group contributed to the evolution of SCCmec: S. vitulinus and S. fleurettii contributed to the assembly of the mec complex, and S. sciuri most likely provided the mobile element in which mecA was later incorporated. We hypothesize that an ancestral SCCmec III cassette (an element carried by one of the most epidemic methicillin-resistant S. aureus clones) originated in S. sciuri possibly by a recombination event in a human host or a human-created environment and later was transferred to S. aureus.
| S-EPMC5444190 | biostudies-literature
Project description:Bacterial viruses (phages) and the immune systems targeted against them significantly impact bacterial survival, evolution, and the emergence of pathogenic strains. While recent research has made spectacular strides towards discovering and validating new defenses in a few model organisms1-3, the inventory of immune systems in clinically-relevant bacteria remains underexplored, and little is known about the mechanisms by which these systems horizontally spread. Such pathways not only impact the evolutionary trajectory of bacterial pathogens, but also threaten to undermine the effectiveness of phage-based therapeutics. Here, we investigate the battery of defenses in staphylococci, opportunistic pathogens that constitute leading causes of antibiotic-resistant infections. We show that these organisms harbor a variety of anti-phage defenses encoded within/near the infamous SCC (staphylococcal cassette chromosome) mec cassettes, mobile genomic islands that confer methicillin resistance. Importantly, we demonstrate that SCCmec-encoded recombinases mobilize not only SCCmec, but also tandem cassettes enriched with diverse defenses. Further, we show that phage infection potentiates cassette mobilization. Taken together, our findings reveal that beyond spreading antibiotic resistance, SCCmec cassettes play a central role in disseminating anti-phage defenses. This work underscores the urgent need for developing adjunctive treatments that target this pathway to save the burgeoning phage therapeutics from suffering the same fate as conventional antibiotics.
| S-EPMC10055296 | biostudies-literature
Project description:A pivotal event in the evolutionary path of methicillin-resistant Staphylococcus aureus (MRSA) is the acquisition of the staphylococcal cassette chromosome mec (SCCmec) element carrying the mecA gene, the determinant of methicillin resistance. Community-acquired (CA) MRSA is commonly associated with skin/soft tissue infections, and doxycycline is one of the drug choices for this purpose. Doxycycline resistance is associated with the acquisition of the tetK gene carried by the S. aureus plasmid pT181, which may also be integrated into SCCmec III and V. The aim of this study was to describe a novel SCCmec IV subtype (IVm) carrying tetK and reveal the genetic context of this element. The SCCmec sequence was obtained by whole-genome sequencing of the MRSA strain 2288 (ST1 CA-MRSA) and genomic analysis performed using different bioinformatics tools. A copy of pT181 was found to be integrated in the new SCCmec IVm of the strain 2288. The SCCmec IVm has high nucleotide identity (99%) with SCCmec IVa of the strain MW2, except for the J3 region, where the pT181 - carrying tetK gene - is inserted. Inverted repeats (IRs) flanking pT181 were found in this region, suggesting the occurrence of recombination events. The strain 2288 (spa type t125) shares most of the virulence attributes with MW2 (spa type t128), which is recognized in the past as a cause of severe infections in children in USA. The pattern of branching in the phylogenetic tree depicts a recent common ancestor shared by the 2228 strain and other MRSA from USA, including ERS410852, TCH70, CIG1835, CO-41, MW2, and USA400-0051, but none of them carried pT181. This study also showed that the tetK carried by SCCmec IVm is functional, determining resistance to doxycycline and tetracycline. The potential dissemination of the tetK and mecA genes in the same genetic event by the acquisition of this new SCCmec subtype is of concern for community infections.
| S-EPMC6299468 | biostudies-literature
Project description:Background and objectivesMRSA became a widely recognized cause of mortality worldwide with necessity of its epidemiological pattern study. Typing of MRSA isolates was performed molecularly based on SCCmec type and relation to resistance pattern was investigated.Materials and methodsOut of 200 clinical specimens, S. aureus was detected phenotypically and confirmed as MRSA by PCR in 124 isolates obtained from associated laboratories of different hospitals of Zagazig, during 2018-2019. Antimicrobial resistance pattern was detected and MRSA SCCmec was typed by two methods.ResultsS. aureus rate was high in wounds, sputum, blood, and urine isolates. Antimicrobial resistance rates against cefotaxime, tetracycline, gentamicin, ciprofloxacin, erythromycin, azithromycin, clindamycin, chloramphenicol, sulfamethoxazole-trimethoprim, linezolid and vancomycin were 82.3%, 65.3%, 56.4%, 45.1%, 37.1%, 32.3%, 32.3%, 25%, 7.3%, 2.4% and 0%, respectively. Multiplex-PCR(M-PCR) was able to detect SCCmec element among 57% of isolates classified as SCCmec II (n=40), III (n=21), IVa (n=3), IVd (n=2), V(n=1), and four isolates contain both SCCmec II and SCCmec IV. Traditional typing by PCR for mec and ccr gene complexes was almost concordant with M-PCR. Furthermore, it was able to identify SCCmec types VI, IX, and XIV among 1, 3 and 18 isolates, respectively. No Statistical correlation was established between type of cassette and rate of antimicrobial resistance. Phylogenetic analysis reveals that all ccr types were related to each other and no significant variation in the same ccr type of different SCCmec cassettes.ConclusionMost MRSA isolates were MDR reflecting antimicrobials misuse. Detection of various SCCmec types among MRSA isolates indictae the complexity of MRSA epidemiology and increase chance for gene sharing creating new types. The presented investigation was important in understanding MRSA epidemiology and diversity in Egypt providing advice for improving therapeutic protocols.
| S-EPMC9085552 | biostudies-literature
Project description:The introduction of living donor liver transplantation (LDLT) has been one of the most remarkable steps in the field of liver transplantation (LT). First introduced for children in 1989, its adoption for adults has followed only 10 years later. As the demand for LT continues to increase, LDLT provides life-saving therapy for many patients who would otherwise die awaiting a cadaveric organ. In recent years, LDLT has been shown to be a clinically safe addition to deceased donor liver transplantation (DDLT) and has been able to significantly extend the scarce donor pool. As long as the donor shortage continues to increase, LDLT will play an important role in the future of LT.
| S-EPMC2131378 | biostudies-other
Project description:Living cells implement complex computations on the continuous environmental signals that they encounter. These computations involve both analogue- and digital-like processing of signals to give rise to complex developmental programs, context-dependent behaviours and homeostatic activities. In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately. Here we integrate analogue and digital computation to implement complex hybrid synthetic genetic programs in living cells. We present a framework for building comparator gene circuits to digitize analogue inputs based on different thresholds. We then demonstrate that comparators can be predictably composed together to build band-pass filters, ternary logic systems and multi-level analogue-to-digital converters. In addition, we interface these analogue-to-digital circuits with other digital gene circuits to enable concentration-dependent logic. We expect that this hybrid computational paradigm will enable new industrial, diagnostic and therapeutic applications with engineered cells.
| S-EPMC4895730 | biostudies-literature
Project description:The epidemiology of Panton-Valentine leukocidin (PVL)-positive MRSA in community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was examined. Three hundred and forty-two CA-MRSA strains that were susceptible to imipenem and cefazolin were isolated from 1107 samples (intravenous catheter, blood, sputum, urine, skin, wound, and pharynx) from outpatients at Showa University Hospital in Japan between September 2009 and March 2017. The PVL gene was detected in 46 of 342 CA-MRSA strains, accounting for 13.5%. The type of SCCmec was determined by detection of each SCCmec-specific region, class complex, and ccr. SCCmec type IV comprised 33 strains, type V comprised 5 strains, type VII comprised 4 strains, and the unclassified type comprised 4 strains. Among the type IV strains, subtype IVa was dominant, comprising 23 of 33 strains, and the remaining 10 strains were of varying subtypes. The SCCmec type III-specific region, CZ049, was amplified in 2 type V strains, 4 type VII strains, and 4 unclassified strains. In 4 unclassified strains, CZ049 and ccr5 were detected, but neither the SCCmec-specific region nor class complex was detected. The PVL-positive rate was lower than that in Western countries. The SCCmec types of PVL-positive CA-MRSA strains were found to vary, indicating a diverse spreading route.
| S-EPMC6441793 | biostudies-literature
Project description:Antimicrobial resistance in Staphylococcus spp. colonising the nasopharynx can create risk factors of therapeutic treatment failure or prophylaxis in pregnant women. Resistance is mostly encoded on plasmids (e.g., blaZ gene for penicillinase synthesis) or chromosomes (e.g., mecA and mecC for methicillin resistance). The mecA gene is part of the chromosomal mec gene cassette (SCCmec), which is also located on the plasmid. The disc diffusion method for the selected drugs (beta-lactams, fluoroquinolones, streptogramins, aminoglicosides, macrolides, oxasolidinones, tetracyclines and other groups) was used. PCR for blaZ, mecA and mecC genes and SCCmec cassette detection and typing were performed. S. aureus (54.4%) and S. epidermidis (27.9%) were the most prevalent and showed the highest diversity of resistance profiles. The blaZ, mecA and mecC genes were reported in 95.6%, 20.6% and 1.5% of isolates, respectively. The highest resistance was found to beta-lactams, commonly used during pregnancy. Resistance to a variety of antimicrobials, including benzylpenicillin resistance in blaZ-positive isolates, and the existence of a very high diversity of SCCmec cassette structures in all staphylococci selected from the nasopharyngeal microbiota of pregnant women were observed for the first time. Knowledge of the prevalence of antimicrobial-resistant staphylococci in the nasopharynx of pregnant women may be important for the appropriate treatment or prophylaxis of this group of patients.
| S-EPMC10178740 | biostudies-literature
Project description:Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) with ST8/SCCmecIV threatens human health. However, its pathogenesis remains unclear. ST8 CA-MRSA (CA-MRSA/J) with SCCmecIVl, which carries the large LPXTG-motif-containing putative adhesin gene, spj, has emerged in Japan. We present the first reported case of death from CA-MRSA/J. The patient was a 64-year-old woman with iliopsoas abscesses complicated by septic pulmonary embolism and multiorgan abscesses. Vancomycin, arbekacin, daptomycin and rifampicin were ineffective. CA-MRSA/J was resistant to erythromycin, clindamycin and antiseptics and was invasive in a HEp-2 cell assay, in contrast to skin-derived villous-adherent CA-MRSA/J. This suggests the strongly invasive pathotype of CA-MRSA/J.
| S-EPMC6141726 | biostudies-literature
Project description:Previous research on methicillin susceptible Staphylococcus aureus (MSSA) belonging to livestock-associated (LA-) sequence type (ST) 398, isolated from pigs and their local surroundings, indicated that differences between these MSSA and their methicillin resistant predecessors (MRSA) are often limited to the absence of the staphylococcal cassette chromosome mec (SCCmec) and few single nucleotide polymorphisms. So far, our understanding on how LA-MRSA endure the environmental conditions associated with pig-farming as well as the putative impact of this particular environment on the mobilisation of SCCmec elements is limited. Thus, we performed in-depth genomic and transcriptomic analyses using the LA-MRSA ST398 strain IMT38951 and its methicillin susceptible descendant. We identified a mosaic-structured SCCmec region including a putative replicative SCCmecVc which is absent from the MSSA chromosome through homologous recombination. Based on our data, such events occur between short repetitive sequences identified within and adjacent to two distinct alleles of the large cassette recombinase genes C (ccrC). We further evaluated the global transcriptomic response of MRSA ST398 to particular pig-farm associated conditions, i.e., contact with host proteins (porcine serum) and a high ammonia concentration. Differential expression of global regulators involved in stress response control were identified, i.e., ammonia-induced alternative sigma factor B-depending activation of genes for the alkaline shock protein 23, the heat shock response and the accessory gene regulator (agr)-controlled transcription of virulence factors. Exposure to serum transiently induced the transcription of distinct virulence factor encoding genes. Transcription of genes reported for mediating the loss of methicillin resistance, especially ccrC, was not significantly different compared to the unchallenged controls. We concluded that, from an evolutionary perspective, bacteria may save energy by incidentally dismissing a fully replicative SCCmec element in contrast to the induction of ccr genes on a population scale. Since the genomic SCCmec integration site is a hot-spot of recombination, occasional losses of elements of 16 kb size may restore capacities for the uptake of foreign genetic material. Subsequent spread of resistance, on the other hand, might depend on the autonomous replication machinery of the deleted SCCmec elements that probably enhance chances for reintegration of SCCmec into susceptible genomes by mere multiplication.
| S-EPMC9728531 | biostudies-literature