has acquired resistance to nearly all antibiotics used in clinical practice. Whereas some resistance mechanisms are conferred by uptake of resistance genes, others evolve by mutation. In this study, IS has been shown to play a role, e.g., in strains displaying intermediate resistance to vancomycin (VISA). To characterize the IS insertion sites in the genomes of two closely related sequence type 247 (ST247) VISA strains, all insertions were mapped in both VISA and a susceptible control strain. The results showed that the three ST247 strains contained the highest number so far of IS insertions for all sequenced strains. Furthermore, in contrast to the case with the other IS elements in these genomes, the IS insertion sites were not identical in the closely related strains, indicating a high transposition frequency of IS When IS was introduced into a laboratory strain which was then cultured in the presence of antibiotics, it was possible to isolate small-colony variants (SCVs) that possessed IS insertions in and that displayed increased resistance to vancomycin and aminoglycosides, respectively. For these clones, a very rapid reversion to the wild type that resembled the fast reversion of clinical SCVs was observed. The reversion was caused by excision of IS in a small number of fast-growing clones that quickly outcompeted the SCVs in broth cultures. In conclusion, the presence of IS confers a strong genomic plasticity that is useful for adaptation to antibiotic stress.
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http://dx.doi.org/10.1128/AAC.00144-17 | DOI Listing |
Microorganisms
December 2024
Centre of Biological Engineering, LIBRO-Laboratório de Investigação em Biofilmes Rosário Oliveira, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
is a major cause of chronic respiratory infections in patients with cystic fibrosis (CF), with biofilm formation contributing to its persistence and antibiotic resistance. This study aimed to gain insights into the mechanistic action of succinic acid as a ciprofloxacin adjuvant against clinically relevant CF isolates, including small colony variants and mucoid strains, and a ciprofloxacin-resistant strain grown within CF dense mucus. Time-kill assays in artificial CF mucus, along with planktonic and surface-attached biofilm experiments, were used to assess the activity of succinic acid alone and in combination with sublethal ciprofloxacin concentrations.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Small colony variant (SCV) is strongly linked to antibiotic resistance and the persistence of osteomyelitis. However, the intrinsic phenotypic instability of SCV has hindered a thorough investigation of its pathogenic mechanisms. In this study, phenotypically stable SCV strains are successfully recovered from clinical specimens, characterized by elevated drug resistance and reduced immunogenicity.
View Article and Find Full Text PDFJAC Antimicrob Resist
December 2024
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Background: Ivacaftor exhibits anti-staphylococcal properties but does not clear from the lungs of people with cystic fibrosis (pwCF). We assessed whether exposure to therapeutic concentrations of ivacaftor could allow to form small colony variants (SCVs), a phenotype commonly associated with bacterial persistence.
Methods: Humanized G551D-CFTR (hG551D) rats were treated with ivacaftor for 7 days.
Injury
November 2024
Department of Trauma Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany. Electronic address:
Soft tissue and bone infections continue to be a serious complication in orthopedic and trauma surgery. Both can lead to a high burden for the patients and the healthcare system. Musculoskeletal infections can be induced by intraoperative contamination, bacterial contamination of open wounds or hematogenous bacterial spread.
View Article and Find Full Text PDFAm J Pathol
October 2024
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:
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