Survival and Intra-Nuclear Trafficking of Burkholderia pseudomallei: Strategies of Evasion from Immune Surveillance?

Vadivelu, Jamuna; Vellasamy, Kumutha Malar; Thimma, J.; Mariappan, Vanitha; Kang, Wen-Tyng; Choh, Leang-Chung; Shankar, Esaki Muthu; Wong, Kum Thong

doi:10.1371/journal.pntd.0005241

Cited by 13 publications

(13 citation statements)

References 29 publications

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“…By contrast, high antibody titres detected in patients years after an episode of acute melioidosis suggest continuous exposure or covert sequestration (bacteria hiding in cryptic sites with downregulation of products) 91 . B. pseudomallei has been found within the nucleus, which could potentially act as a persistence site for later recrudescence 92 . Strain variability or small colony variants could also play a part in determining whether latent or persistent infection is established 93 .…”

Section: B Pseudomallei Infectionmentioning

confidence: 99%

Melioidosis

Wiersinga

Virk

Torres

et al. 2018

Nat Rev Dis Primers

530

792

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Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.

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Section: B Pseudomallei Infectionmentioning

confidence: 99%

Melioidosis

Wiersinga

Virk

Torres

et al. 2018

Nat Rev Dis Primers

530

792

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“…BipC, an immunoreactive protein, is involved in actin binding to facilitate internalization of B. pseudomallei into host cells, as a bipC mutant was impaired in adherence, invasion, and intracellular survival in epithelial cells, and BipC protein is required for full virulence in a murine model of melioidosis [ 78 , 79 ]. Recently, Vadivelu et al [ 80 ] showed that B. pseudomallei localized within the nuclear compartment of host cells, suggesting that the nucleus may play a role as an occult or transient niche for persistence of intracellular pathogens, potentially leading to recurrent episodes or recrudescence of infection.…”

Section: Molecular Pathogenesis Of B Pseudomalleimentioning

confidence: 99%

Melioidosis in Malaysia: Incidence, Clinical Challenges, and Advances in Understanding Pathogenesis

et al. 2018

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Malaysia is an endemic hot spot for melioidosis; however, a comprehensive picture of the burden of disease, clinical presentations, and challenges faced in diagnosis and treatment of melioidosis is not available. This review provides a nonexhaustive overview of epidemiological data, clinical studies, risk factors, and mortality rates from available literature and case reports. Clinical patterns of melioidosis are generally consistent with those from South and Southeast Asia in terms of common primary presentations with diabetes as a major risk factor. Early diagnosis and appropriate management of Malaysian patients is a key limiting factor, which needs to be addressed to reduce serious complications and high mortality and recurrence rates. Promoting awareness among the local healthcare personnel is crucial to improving diagnostics and early treatment, as well as educating the Malaysian public on disease symptoms and risk factors. A further matter of urgency is the need to make this a notifiable disease and the establishment of a national melioidosis registry. We also highlight local studies on the causative agent, Burkholderia pseudomallei, with regards to bacteriology and identification of virulence factors as well as findings from host–pathogen interaction studies. Collectively, these studies have uncovered new correlations and insights for further understanding of the disease.

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“…Future experiments should thus reveal the mechanisms of persistent haemoplasma infection. In particular, it is important to understand whether (a) the low stable infection levels result from the bacterium's or the mammalian host's actions, (b) the bacterium hides in other tissues in the rodent's body (Novacco, Riond, Meli, Grest, & Hofmann-Lehmann, 2013;Tasker et al, 2009a;Wolf-Jäckel et al, 2012), and (c) the bacterium replicates during the stabilized infection period or remains in a dormant state (Mandell & Beverley, 2017;Monack & Hultgren, 2013;Potgieter, Bester, Kell, & Pretorius, 2015;Vadivelu et al, 2017).…”

Section: Infection Dynamicsmentioning

confidence: 99%

Haemoplasmas in wild rodents: Routes of transmission and infection dynamics

et al. 2018

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The way that some parasites and pathogens persist in the hostile environment of their host for long periods remains to be resolved. Here, longitudinal field surveys were combined with laboratory experiments to investigate the routes of transmission and infection dynamics of such a pathogen-a wild rodent haemotropic bacterium, specifically a Mycoplasma haemomuris-like bacterium. Fleaborne transmission, direct rodent-to-rodent transmission and vertical transmission from fleas or rodents to their offspring were experimentally quantified, and indications were found that the main route of bacterial transmission is direct, although its rate of successful transmission is low (~20%). The bacterium's temporal dynamics was then compared in the field to that observed under a controlled infection experiment in field-infected and laboratory-infected rodents, and indications were found, under all conditions, that the bacterium reached its peak infection level after 25-45 days and then decreased to low bacterial loads, which persist for the rodent's lifetime. These findings suggest that the bacterium relies on persistency with low bacterial loads for long-term coexistence with its rodent host, having both conceptual and applied implications.

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Survival and Intra-Nuclear Trafficking of Burkholderia pseudomallei: Strategies of Evasion from Immune Surveillance?

Cited by 13 publications

References 29 publications

Melioidosis

Melioidosis

Melioidosis in Malaysia: Incidence, Clinical Challenges, and Advances in Understanding Pathogenesis

Haemoplasmas in wild rodents: Routes of transmission and infection dynamics

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