We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.

The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment

Staphylococcus lugdunensis has gained recognition as an atypically virulent pathogen with a unique microbiological and clinical profile. S. lugdunensis is coagulase negative due to the lack of production of secreted coagulase, but a membrane-bound form of the enzyme present in some isolates can result in misidentification of the organism as Staphylococcus aureus in the clinical microbiology laboratory. S. lugdunensis is a skin commensal and an infrequent pathogen compared to S. aureus and S. epidermidis, but clinically, infections caused by this organism resemble those caused by S. aureus rather than those caused by other coagulase-negative staphylococci. S. lugdunensis can cause acute and highly destructive cases of native valve endocarditis that often require surgical treatment in addition to antimicrobial therapy. Other types of S. lugdunensis infections include abscess and wound infection, urinary tract infection, and infection of intravascular catheters and other implanted medical devices. S. lugdunensis is generally susceptible to antimicrobial agents and shares CLSI antimicrobial susceptibility breakpoints with S. aureus. Virulence factors contributing to this organism's heightened pathogenicity remain largely unknown. Those characterized to date suggest that the organism has the ability to bind to and interact with host cells and to form biofilms on host tissues or prosthetic surfaces.

From Clinical Microbiology to Infection Pathogenesis: How Daring To Be Different Works for Staphylococcus lugdunensis

Are coagulase-negative staphylococci virulent?

Human-pathogenic bacteria that are able to cause persistent infections must have developed mechanisms to resist the immune defense system. Lysozyme, a cell wall-lytic enzyme, is one of the first defense compounds induced in serum and tissues after the onset of infection. Recently, we showed that Staphylococcus aureus is resistant to lysozyme by O acetylating its peptidoglycan (PG) by O-acetyltransferase (OatA). We asked the question of which staphylococcal species PG is O acetylated. We applied various methods, such as genome analysis, PCR, Southern blotting, lysozyme sensitivity assay, and verification of O acetylation of PG by high-performance liquid chromatography (HPLC) analysis. PCR analysis using S. aureus-derived oatA primers and Southern blotting did not yield reliable results with other staphylococcal species. Therefore, we used the HPLC-based assay to directly detect PG O acetylation. Our studies revealed that the muramic acid was O acetylated only in pathogenic, lysozyme-resistant staphylococci (e.g., S. aureus, S. epidermidis, S. lugdunensis, and others). All nonpathogenic species were lysozyme sensitive. They can be divided into sensitive species (e.g., S. carnosus, S. gallinarum, and S. xylosus) and hypersensitive species (e.g., S. equorum, S. lentus, and S. arlettae). In all lysozyme-sensitive species, the analyzed PG was de-O-acetylated. When we transformed the oatA gene from lysozyme-resistant S. aureus into S. carnosus, the corresponding transformants also became lysozyme resistant.

https://iai.asm.org/content/iai/74/8/4598.full.pdf

The Presence of Peptidoglycan O-Acetyltransferase in Various Staphylococcal Species Correlates with Lysozyme Resistance and Pathogenicity

Background/Purpose Infective endocarditis caused by Staphylococcus lugdunensis is a rare disease Since its first description in 1988, there have only been a few reports of this disease and the causative organism These publications were primarily case reports and brief case series We conducted a literature review to identify the nature of the disease and its risk factors Methods We retrospectively reviewed the cases reported between 1988 and 2008 by searching the relevant literature using the keywords "endocarditis" and " Staphylococcus lugdunensis " in the Medline database All cases included met the definition of the modified Duke criteria Results For the period 1988-2008, 67 cases from 27 articles were reviewed The mean age of individuals was 539 years Left-sided valvular endocarditis represented 52 (825%) of cases and native-valve endocarditis was evident in 48 (787%) of cases A large proportion (82%) of 50 S lugdunensis strains were susceptible to penicillin Valve replacement operations were performed in 42 (667%) patients and the mortality rate was 388% Univariate analysis showed a higher mortality rate in patients aged more than 50 years, those treated before 1995, those treated with antibiotics alone, and those with growth not detected by echocar-diography Medical treatment alone was the independent risk factor for mortality by multivariate analysis Conclusion S lugdunensis endocarditis led to substantial morbidity and mortality Detailed microbiological identification, echocardiography evaluation, and valve replacement may improve the clinical outcome of individuals with S lugdunensis endocarditis

Staphylococcus lugdunensis Infective Endocarditis: A Literature Review and Analysis of Risk Factors

We report a chronic hip arthroplasty infection with Rothia mucilaginosa, a Gram-positive germ belonging to the normal flora of the human oral cavity. Successful treatment was achieved by a two-stage hip arthroplasty revision and intravenous administration of vancomycin. This case report illustrates the potential virulence of R. mucilaginosa in patients with a joint prosthesis. We propose to routinely perform specific staining and prolonged culturing techniques for unusual germs such as Rothia mucilaginosa when the clinical history, physical examination or intra-operative findings suggest an implant infection. This paper reviews current antibiotic prophylaxis guidelines for infection prevention of joint arthroplasties during dental procedures.

Late prosthetic joint infection due to Rothia mucilaginosa.

Failure of cefotaxime and meropenem to eradicate meningitis caused by an intermediately susceptible Streptococcus pneumoniae strain.

Transient bacteremia with Aureobacterium spp., a yellow pigmented coryneform organism frequently confused with “Corynebacterium aquaticum”

Yersinia pseudotuberculosis: a rare cause of septicemia

Described here are three cases of acute native valve endocarditis due to the coagulase-negative pathogen Staphylococcus lugdunensis with serious complications. Two of the three patients died despite optimal antibiotic therapy and cardiovascular surgery. These cases demonstrate the aggressive nature of S. lugdunensis and emphasize the importance of identifying coagulase-negative staphylococci to the species level and not considering the isolation of S. lugdunensis from normally sterile body fluids as contamination. On the contrary, when this organism is found in patients with endocarditis, early surgery should be considered. The possibility that this organism could be misidentified as S. aureus because of "autocoagulation" and that commercial identification systems may misidentify it as S. haemolyticus, S. hominis or S. warneri should also be remembered.

Three cases of destructive native valve endocarditis caused by Staphylococcus lugdunensis

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