Comment

Reducing the melioidosis burden: public health, chronic disease prevention, or improved case management?

The present study reported a rare gentamicin-susceptible β-lactamase (PenA, OXA-57) expressing clinical Burkholderia pseudomallei isolate VB29710 from India. Whole-genome sequencing and structural analyses revealed the insertion of R962 and L963 into AmrB, the transmembrane-protein of the AmrAB-OprA efflux-pump that affected aminoglycoside-efflux through local alterations in backbone conformation.

Melioidosis is caused by the environmental bacterium Burkholderia pseudomallei. South Asia is estimated to have 44% of the global disease burden. Among South Asian countries, Bangladesh and Sri Lanka are considered endemic for melioidosis; a few cases have been reported from Nepal, and a few imported cases from Pakistan have also been reported. India has experienced an increase in numbers of melioidosis cases in the recent years. The bacteria is inherently present in the soil and enters the human body via skin abrasions, inhalation, or ingestion. As clinicians are often ignorant about the similar characteristics of this disease and several other common tropical diseases, it causes a major delay in the timely diagnosis and management. The organism is easily mistaken as Pseudomonas spp in microbiology laboratories and may be dismissed as a common laboratory contaminant. The poor diagnostic sensitivity of blood culture also leads to missed diagnosis. Hence, both clinical ignorance and missed laboratory diagnosis have misrepresented melioidosis as a rare entity. The key preventive interventions are avoiding contact with loose and muddy soils of meliodosis-endemic areas, and provision of safe drinking water. The present article describes the various possible attributes for melioidosis underdiagnosis and the challenges of improving the diagnosis in conjunction with viable solutions.

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Melioidosis is a tropical infection caused by the soil bacterium Burkholderia pseudomallei. Despite the substantial impact of this often overlooked pathogen on both the health-care systems and economies of numerous low-income and middle-income countries around the world, melioidosis is not officially classified as a neglected tropical disease (NTD) by WHO. Melioidosis causes a higher estimated disease burden and mortality than many other recognised NTDs, with deaths primarily occurring among rural poor populations in low-income and middle-income countries. Fortunately, the impact of melioidosis in a region can be reduced once awareness is established of its known or suspected endemicity. In this Personal View, we provide evidence in support of official recognition of melioidosis as an NTD. We urge member states to request that WHO revisit their NTD list and appeal to government and philanthropic organisations to establish programmes in endemic countries to control melioidosis in order to reduce its global health burden.

Burkholderia pseudomallei is regarded as a global threat because of its ability to cause melioidosis, and potential as bioweapon. Intrinsic resistance to frontline antibiotics remains a major challenge in treating melioidosis. The increasing global burden of B. pseudomallei triggers the need to develop effective drugs and vaccine for controlling this pathogen. Therefore, we analyzed the whole proteome of B. pseudomallei K96243 using subtractive proteomic and immune-informatic analysis to find out potential drug target and vaccine candidate. Our analysis revealed 45 essential and non-homologous metabolic proteins, involved in different unique metabolic pathways. 36 out of 45 proteins can serve as novel drug targets and the remaining proteins had already been targeted with experimental drugs. 2 novel targets of cytoplasmic localization, namely dihydroneopterin aldolase and phosphoribosyl transferase were subjected to molecular docking with 14 antibiotics, which revealed the strong binding affinity of cefiderocol and tetracycline to the identified targets. Moreover, 100 ns molecular dynamic simulation and MM-PBSA calculation revealed the stability of drug-protein complexes. On the contrary, highly antigenic, non-allergic and non-toxic epitopes from three essential outer membrane proteins were joined by linkers and adjuvant to construct a chimeric peptide vaccine. The vaccine construct could efficiently bind to TLR-4 and generated robust immune response. The vaccine-receptor complex showed minimum deformability and good stability. Overall, our findings will aid in designing new inhibitors that disrupts the functionality of proposed targets and in the development of subunit vaccine for the therapeutic and prophylactic management of B. pseudomallei.