Burkholderia pseudomallei: A Multifaceted Threat and the Path Forward in Treatment and Prevention.

Abstract

Burkholderia pseudomallei, a gram-negative facultative intracellular bacterium, is the causative agent of melioidosis, a life-threatening infectious disease endemic to tropical and subtropical regions, particularly Southeast Asia and Northern Australia. Key risk factors such as diabetes, alcoholism, and socioeconomic challenges were identified as major contributors to disease susceptibility and treatment outcomes in melioidosis. Globally, melioidosis accounts for approximately 89,000 deaths annually and poses a significant public health concern, particularly in resource-limited settings. B. pseudomallei exhibits remarkable environmental resilience, thrives in soil and water, and is intrinsically resistant to various antibiotics. Its pathogenicity is mediated by diverse virulence factors, including type III and VI secretion systems, a protective capsule, lipopolysaccharide (LPS), and BimA-mediated actin-based motility, which facilitate intracellular survival, immune evasion, and systemic dissemination. This bacterium can cause a wide spectrum of clinical manifestations ranging from localized skin infections to severe septicemia, pneumonia, and neurological involvement. In certain cases, B. pseudomallei may persist in a latent state for years and reactivation is often triggered by immunosuppression. The treatment of melioidosis is challenging because of its intrinsic antibiotic resistance, necessitating a two-phase approach: an intensive phase with intravenous antibiotics, such as ceftazidime or meropenem, followed by a prolonged eradication phase using trimethoprim-sulfamethoxazole. However, relapse remains a concern, particularly in patients with poor adherence to the therapy. Preventive strategies, particularly in endemic regions, focus on minimizing environmental exposure through protective measures and safe water practices. Despite advancements in therapeutic approaches, there is an urgent need for novel treatment strategies, including bacteriophage therapy and vaccine development, to enhance melioidosis prevention and control. Understanding the complex pathogenic mechanisms of B. pseudomallei is essential to improve its clinical management and reduce its global burden.