Professional phagocytic cells such as macrophages are a central part of innate immune defence. They ingest microorganisms into membrane-bound compartments (phagosomes), which acidify and eventually fuse with lysosomes, exposing their contents to a microbicidal environment. Gram-positive Rhodococcus equi can cause pneumonia in young foals and in immunocompromised humans. The possession of a virulence plasmid allows them to subvert host defence mechanisms and to multiply in macrophages. Here, we show that the plasmid-encoded and secreted virulenceassociated protein A (VapA) participates in exclusion of the proton-pumping vacuolar-ATPase complex from phagosomes and causes membrane permeabilisation, thus contributing to a pH-neutral phagosome lumen. Using fluorescence and electron microscopy, we show that VapA is also transferred from phagosomes to lysosomes where it permeabilises the limiting membranes for small ions such as protons. This permeabilisation process is different from that of known membrane pore formers as revealed by experiments with artificial lipid bilayers. We demonstrate that, at 24 hr of infection, virulent R. equi is contained in a vacuole, which is enriched in lysosome material, yet possesses a pH of 7.2 whereas phagosomes containing a vapA deletion mutant have a pH of 5.8 and those with virulence plasmid-less sister strains have a pH of 5.2. Experimentally neutralising the macrophage endocytic system allows avirulent R. equi to multiply. This observation is mirrored in the fact that virulent and avirulent R. equi multiply well in extracts of purified lysosomes at pH 7.2 but not at pH 5.1. Together these data indicate that the major function of VapA is to generate a pH-neutral and hence growth-promoting intracellular niche. VapA represents a new type of Gram-positive virulence factor by trafficking from one subcellular compartment to another, affecting membrane permeability, excluding proton-pumping ATPase, and consequently disarming host defences.
The minimal anterolateral acromial approach offers a less invasive access to the proximal humerus. Functional impairment following this procedure may be caused by paresis of the deltoid muscle as a result of iatrogenic injury to the axillary nerve. It was addressed whether electromyography (EMG) of the deltoid muscle gives evidence for an axillary nerve lesion in association with the minimal anterolateral acromial approach.Twenty-three patients (14 men, 9 women; average age 58 years) with proximal humerus fractures were included in this clinical observation. Follow-up was performed 6 weeks (6w), 6 months (6m) and 12 months (12m) postoperatively. EMG changes indicating either lesion of the axillary nerve or direct muscle trauma were distinguished in “acute”, “chronic” and “combined” and semi quantified in “slight”, “moderate” and “severe”. Patients were examined clinically (standard neurological examination and Constant Score).Three cases of incomplete axillary nerve lesion with limited functional impairment were detected. Subclinical EMG signs of neural impairment of the deltoid muscle were observed frequently (6w, N = 8; 6m, N = 8; 12m, N = 7). Functional outcome did not show an association with EMG.Most patients presented with subclinical and most likely trauma- related neurogenic lesions of the deltoid muscle following the anterolateral acromial approach. Despite the fact that the axillary nerve does not function normally following this less-invasive approach for fixation of proximal humerus fractures, this does not appear to affect the clinical outcome. Prospective studies with larger sample sizes are required to determine the effect of axillary nerve retraction in the more commonly used deltopectoral approach.
Rhodococcus equi (Prescotella equi;Sangal et al., 2022) is a Grampositive actinomycete, a close relative of pathogenic mycobacteria, and both an environmental soil bacterium and a facultative intracellular pathogen. It can cause life-threatening pulmonary infections in young foals and in immunocompromised humans, particularly in
Rhodococcus equi
is a major cause of life-threatening pneumonia in foals and occasionally in immunocompromised persons. Virulence-associated protein A (VapA) promotes
R. equi
multiplication in lung macrophages, which are the major host cells during foal infection.
Millions of tons small plastic pieces (microplastic) find their way into the environment every year. They pose digestive and toxicity problems to various life forms in soil, freshwater, and seawater.
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