Antimicrobial Activity of Neutrophils Against Mycobacteria

The mycobacterium genus contains a broad range of species, including the human pathogens M. tuberculosis and M. leprae. These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage.

Spectrum of mycobacterial pathogens responsible for head and neck tuberculosis-like presentation

Tuberculosis (TB) of the head and neck can be contained in the lymph nodes, larynx, oropharynx, salivary glands, nose and paranasal sinuses, ear, skin and skull. Head and neck TB presentations are varied in nature and thus difficult to diagnose. The clinical features, radiological findings, microbiological diagnostic modalities, surgical and medical management and outcomes of nine cases of head and neck TB are discussed in detail here, together with a thorough review of the literature. Patients presented with atypical symptoms such as discharging sinus, ear lobule swelling, otitis media, vision loss and facial weakness, long refractory otorrhoea and granulation tissue in the ear canal. We diagnosed tubercular skull base osteomyelitis (one case) and laryngeal tuberculosis (two cases), mastoid tuberculosis (one case) and non-tubercular mycobacterial infection involving the temporal bone (two cases), sino-nasal region (one case), maxilla (one cases) and ear lobule (one case) over a period of 8 months. All patients were managed successfully with a combination of surgery and a well-planned treatment regimen for non-tuberculous mycobacteria (NTM) or anti-tubercular drugs for TB. All had successful outcomes except one patient with tubercular skull base osteomyelitis who expired before the initiation of anti-tubercular therapy (ATT). High clinical suspicion followed by thorough diagnostic work-up for both TB and NTM would enable early diagnosis and complete treatment.

Non-tuberculous Mycobacterial Infection of the Musculoskeletal System Detected at Two Tertiary Medical Centres in Henan, China, 2016–2020

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal system is rare but poses a grave threat to public health. These infections yield non-specific symptoms that remain undetected until the development of the later stages of the disease. In this study, we performed a retrospective review of 25 cases of musculoskeletal NTM infection at two tertiary medical centres over a 5-year period to determine the clinical features and improve the current clinical diagnosis and treatment. The most common mycobacterial species detected were Mycobacterium fortuitum in eleven patients, Mycobacterium abscessus in eight patients, Mycobacterium houstonense in three patients, Mycobacterium avium in two patients, and Mycobacterium smegmatis in one patient. The sites of infection included the limbs and joints, most commonly the knee (ten patients) and foot (six patients). The median duration from the onset of symptoms to diagnosis was 2.5 months (0.8–13.5 months). Deep sinus tracts extending to the surgical site were observed in 60% of the patients (15/25), and granulomatous inflammation and granulomatous inflammation with necrosis occurred in 60% of the patients (15/25). All patients underwent surgical treatment for infection control, and all patients, except one, received antimycobacterial therapy based on drug sensitivity assays. The median duration of the antimicrobial chemotherapy was 5 months (range: 3–20 months). At the final follow-up, 24 patients presented with absence of recurrence and one patient succumbed owing to heart failure after debridement. Our findings highlight the importance of vigilance and improvements in the diagnostic methods for musculoskeletal NTM infection. Aggressive surgical treatment and antimycobacterial drug treatment can help achieve satisfactory results.

Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages

The host immune system plays a pivotal role in the containment of Mycobacterium tuberculosis (Mtb) infection, and host-directed therapy (HDT) is emerging as an effective strategy to treat tuberculosis (TB), especially drug-resistant TB. Previous studies revealed that expression of sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, was downregulated in macrophages after Mycobacterial infection. Inhibition of SIRT7 with the pan-sirtuin family inhibitor nicotinamide (NAM), or by silencing SIRT7 expression, promoted intracellular growth of Mtb and restricted the generation of nitric oxide (NO). Addition of the exogenous NO donor SNAP abrogated the increased bacterial burden in NAM-treated or SIRT7-silenced macrophages. Furthermore, SIRT7-silenced macrophages displayed a lower frequency of early apoptotic cells after Mycobacterial infection, and this could be reversed by providing exogenous NO. Overall, this study clarified a SIRT7-mediated protective mechanism against Mycobacterial infection through regulation of NO production and apoptosis. SIRT7 therefore has potential to be exploited as a novel effective target for HDT of TB.