IsdC from Staphylococcus lugdunensis Induces Biofilm Formation under Low-Iron Growth Conditions

Staphylococcus lugdunensis is a coagulase-negative staphylococcus that is a commensal of humans and an opportunistic pathogen. It can cause a spectrum of infections, including those that are associated with the ability to form biofilm, such as occurs with endocarditis or indwelling medical devices. The genome sequences of two strains revealed the presence of orthologues of the ica genes that are responsible for synthesis of poly-N-acetylglucosamine (PNAG) that is commonly associated with biofilm in other staphylococci. However, we discovered that biofilm formed by a panel of S. lugdunensis isolates growing in iron-restricted medium was susceptible to degradation by proteases and not by metaperiodate, suggesting that the biofilm matrix comprised proteins and not PNAG. When the iron concentration was raised to 1 mM biofilm formation by all strains tested was greatly reduced. A mutant of strain N920143 lacking the entire locus that encodes iron-regulated surface determinant (Isd) proteins was defective in biofilm formation under iron-limited conditions. An IsdC-null mutant was defective, whereas IsdK, IsdJ, and IsdB mutants formed biofilm to the same level as the parental strain. Expression of IsdC was required both for the primary attachment to unconditioned polystyrene and for the accumulation phase of biofilm involving cell-cell interactions. Purified recombinant IsdC protein formed dimers in solution and Lactococcus lactis cells expressing only IsdC adhered to immobilized recombinant IsdC but not to IsdJ, IsdK, or IsdB. This is consistent with a specific homophilic interaction between IsdC molecules on neighboring cells contributing to accumulation of S. lugdunensis biofilm in vivo.     

Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients

Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.     

The role of macrophage colony-stimulating factor in patients with acute myocardial infarction: a pilot study

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = -.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI.     

Vasospastic angina and scombroid syndrome: a case report

Scombroid syndrome is a fish poisoning characterised by the onset of symptoms compatible with a pseudoallergic reaction; it is rarely also responsible of signs and symptoms of acute coronary syndromes, as demonstrated in this case report.