Staphylococci, with the leading species
and
, are the most frequent causes of infections on indwelling medical devices. The biofilm phenotype that those bacteria adopt during device-associated ...infection facilitates increased resistance to antibiotics and host immune defenses. This review presents and discusses the molecular mechanisms contributing to staphylococcal biofilm development and their in-vivo importance. Furthermore, it summarizes current strategies for the development of therapeutics against staphylococcal biofilm-associated infection.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infection worldwide, including a wide array of both hospital- and community-acquired infections-most commonly bacteremia, ...upper and lower respiratory tract infection, skin and soft-tissue infection, osteomyelitis, and septic arthritis. This chapter describes the epidemiology of MRSA infection, its ability to confer antibiotic resistance and produce a wide array of virulence factors, and its pivotal role in human infection, especially cystic fibrosis. It also provides an introduction to the strategies for treatment of both chronic and acute MRSA infections.
Bacterial infection often results in the formation of tissue abscesses, which represent the primary site of interaction between invading bacteria and the innate immune system. We identify the host ...protein calprotectin as a neutrophil-dependent factor expressed inside Staphylococcus aureus abscesses. Neutrophil-derived calprotectin inhibited S. aureus growth through chelation of nutrient Mn²⁺ and Zn²⁺: an activity that results in reprogramming of the bacterial transcriptome. The abscesses of mice lacking calprotectin were enriched in metal, and staphylococcal proliferation was enhanced in these metal-rich abscesses. These results demonstrate that calprotectin is a critical factor in the innate immune response to infection and define metal chelation as a strategy for inhibiting microbial growth inside abscessed tissue.
Staphylococcus aureus causes a wide range of illnesses, from skin infections and persistent bone infections to life-threatening septicemia and endocarditis. Methicillin-resistant S. aureus (MRSA) is ...one of the most common bacteria that cause nosocomial and community-acquired infections. Clindamycin is one of the most effective treatments for several bacterial infections. Despite this, these infections may develop inducible clindamycin resistance during treatment, leading to treatment failure. This study determined the incidence of inducible clindamycin resistance among S. aureus clinical isolates. A total of 800 S. aureus strains were identified from clinical samples collected from several university hospitals in Egypt. All isolates were examined for the presence of MRSA using cefoxitin (30 μg) and the Kirby Bauer disk diffusion technique. The induction phenotypes of all 800 S. aureus strains were evaluated using the disk approximation test (D test), as recommended by the Clinical and Laboratory Standard Institute. Of the 800 strains of S. aureus, 540 (67.5%) were identified as MRSA and 260 (32.5%) were classified as methicillin-sensitive S. aureus (MSSA). In MRSA infections, clindamycin constitutive and inducible resistance was more frequent than in MSSA infections (27.8% versus 11.5% and 38.9% versus 15.4%, respectively). Clindamycin-sensitive strains were more prevalent in MSSA (53.8%) than in MRSA (20.4%) infections. In conclusion, the frequency of constitutive and inducible clindamycin resistance in MRSA isolates emphasizes the need to use the D test in routine antimicrobial susceptibility testing to evaluate clindamycin susceptibility, as the inducible resistance phenotype can inhibit the action of clindamycin and thus affect treatment efficacy.
To determine the epidemiology, clinical features, and microbiology of adult native joint septic arthritis in Canterbury, New Zealand, over a 5-year period in individuals with and without an ...underlying rheumatic disorder.
Patients with native joint septic arthritis were identified retrospectively and classified by Newman's criteria. The clinical characteristics were described and comparisons made between those with and without underlying rheumatic disease.
Two hundred forty-eight cases of native joint septic arthritis (mean age 60, range 16-97 yrs) were identified with an overall incidence rate of 12.0/100,000/year (95% CI 10.6-13.6). Yearly incidence increased with age to a maximum of 73.4/100,000 in those > 90 years of age. Septic arthritis was iatrogenic in 16.9% of cases while 27% had an underlying inflammatory arthritis including gout (14.9%), calcium pyrophosphate disease (8.5%), and rheumatoid arthritis (4%). Few patients were taking immunosuppressant therapy, with just 1 taking a biological agent. Staphylococcus aureus was the most commonly identified organism. Those with underlying inflammatory arthritis were significantly older (73.6 yrs vs 55.6 yrs; p < 0.001), more likely to be female (55.2% vs 26.0%; p < 0.001), and to have septic polyarthritis (16.4% vs 4.4%; p = 0.002). The 30-day mortality was 2%, increasing to 6% at 90 days.
The incidence of septic arthritis in Canterbury, New Zealand, is higher than in previous studies. Crystal arthropathy commonly coexisted with infection although autoimmune arthritis and immunosuppression was less of a factor than anticipated.
Uninfected diabetes-related foot ulcer (DFU) progression to diabetes-related foot infection (DFI) is a prevalent complication for patients with diabetes. DFI often progresses to osteomyelitis ...(DFI-OM). Active (growing)
is the most common pathogen in these infections. There is relapse in 40-60 % of cases even when the initial treatment at the DFI stage apparently clears infection.
adopts the quasi-dormant Small Colony Variant (SCV) state during DFU and consequently infection, and when present in DFI cases also permits survival in non-diseased tissues as a reservoir to cause relapse.
. The aim of this study was to investigate the bacterial factors that facilitate persistent infections.
People with diabetes were recruited from two tertiary hospitals. Clinical and bacterial data was taken from 153 patients with diabetes (51 from a control group with no ulcer or infection) and samples taken from 102 patients with foot complications to identify bacterial species and their variant colony types, and then compare the bacterial composition in those with uninfected DFU, DFI and those with DFI-OM, of whom samples were taken both from wounds (DFI-OM/W) and bone (DFI-OM/B). Intracellular, extracellular and proximal 'healthy' bone were examined.
was identified as the most prevalent pathogen in diabetes-related foot pathologies (25 % of all samples). For patients where disease progressed from DFU to DFI-OM,
was isolated as a diversity of colony types, with increasing numbers of SCVs present. Intracellular (bone) SCVs were found, and even within uninfected bone SCVs were present. Wounds of 24 % of patients with uninfected DFU contained active
. All patients with a DFI with a wound but not bone infection had previously had
isolated from an infection (including amputation), representing a relapse.
The presence of
SCVs in recalcitrant pathologies highlights their importance in persistent infections through the colonization of reservoirs, such as bone. The survival of these cells in intracellular bone is an important clinical finding supporting
data. Also, there seems to be a link between the genetics of
found in deeper infections compared to those only found in DFU.
Extracellular vesicles (EVs) provide a novel intercellular communication mechanism to transfer biologically important molecules to target cells. Although several pieces of evidence have shown that ...EVs have potential to respond to bacterial infections, our knowledge about the role of circular RNA (circRNA), an important cargo of EV, behind this process remains poor. In particular, the mechanism by which circRNAs are packaged into EVs remains elusive during bacterial infection. In the present study, EVs from bovine milk samples with or without Staphylococcus aureus (S. aureus) infection were isolated. The presence of circRNAs in milk-derived EVs (MEVs) was validated for the first time by PCR amplification with convergent and divergent primers and the RNase R resistance test. Through high-throughput sequencing, the expression profile of circRNAs in EVs was found to be changed during S. aureus infection. Moreover, we demonstrated that circRNAs were selectively packaged into EVs. Finally, bioinformatic analyses predicted the involvement of differentially expressed circRNAs in immune functions. In summary, our findings offer an insight into the packaging mechanism of EV circRNAs and underscore the potential by which host used the EV circRNAs in response to pathogenic bacterial infections.
Currently, methicillin-resistant Staphylococcus aureus (MRSA) is a universal threat. After being well established in the healthcare setting, it has emerged in the community among people with no risk ...factors for MRSA acquisition, therefore imposing a new threat. The subsequent detection of MRSA colonizing or infecting animals as well as in food of animal origin was of major concern, revealing new reservoirs for MRSA. The major MRSA clonal lineages circulating in the different settings, i.e. in hospitals, in the community and among animals, are described here, differentiating between clones colonizing companion and food-chain animals. Particular attention is given to the widely spread livestock-associated MRSA clonal complex (CC) 398, which is mainly associated with professional exposure but may be of high pathogenicity. The recent detection of a mecA homologue, designated mecC, with a wide geographical distribution in Europe, and including a large diversity of hosts (food-chain, companion and wildlife animals and also detected in water samples) adds to the threat. Domestication as well as globalization of the livestock industry have intensified exchanges between human and animal bacteria. We report here several cases of transmission of MRSA between companion or food-chain animals and humans, as well as some MRSA clones of human origin that have adapted to new animal hosts eventually by losing useless virulence factors or acquiring new mobile genetic elements.
The objective of this study was to investigate the evolution of resistance to antimicrobials, corresponding mechanisms and molecular characteristics of Staphylococcus spp., between 1999 and 2014.
...Susceptibility to 38 antimicrobials was determined for 632 clinical staphylococcal isolates obtained from companion animals (dogs, cats, horses and other animals). Twenty antimicrobial resistance genes, including mecA and mecC, were screened by PCR. Methicillin-resistant staphylococci were characterized by spa (Staphylococcus aureus), SCCmec, MLST and PFGE typing. Statistical analyses were performed using SAS v9.3 and differences were considered relevant if P ≤ 0.05.
The mecA gene was identified in 74 staphylococcal isolates (11.6%): 11 MRSA (40.7%), 40 methicillin-resistant Staphylococcus pseudintermedius (MRSP; 8.7%) and 23 methicillin-resistant CoNS (26.7%). Resistance to the majority of antimicrobials and the number of mecA-positive isolates increased significantly over time. Eighteen spa types were identified, including two new ones. MRSA isolates were divided into three PFGE clusters that included ST22-IV, ST105-II, ST398-V and ST5-VI. Most methicillin-resistant Staphylococcus epidermidis isolates were of clonal complex (CC) 5, including a new ST, and clustered in eight PFGE clusters. MRSP were grouped into five PFGE clusters and included ST45-NT, ST71-II-III, ST195-III, ST196-V, ST339-NT, ST342-IV and the new ST400-III. Methicillin-resistant Staphylococcus haemolyticus clustered in two PFGE clusters.
The significant increase in antimicrobial-resistant and mecA-positive isolates in recent years is worrying. Furthermore, several isolates are MDR, which complicates antimicrobial treatment and increases the risk of transfer to humans or human isolates. Several clonal lineages of MRSA and methicillin-resistant S. epidermidis circulating in human hospitals and the community were found, suggesting that companion animals can become infected with and contribute to the dissemination of highly successful human clones. Urgent measures, such as determination of clinical breakpoints and guidelines for antimicrobial use, are needed.
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