Neurological Melioidosis Research Articles

Neuromelioidosis – A retrospective review of thirteen cases from a tertiary care centre from South India

Neurologic melioidosis warrants attention in view of its rarity and lethal consequences. We performed a retrospective review of culture confirmed neurologic melioidosis reported between 2017 and 2023. Thirteen patients were identified with median age 43 years and all but three were males. Brain parenchyma was involved in 57% cases (7/13) as cerebritis, encephalitis and macro abscess or micro abscess. Three patients had myelitis with spinal cord micro abscess and cerebral venous thrombosis in three other patients. Five patients died during hospitalization. Two were discharged against medical advice due to financial constraints. Six survivors were followed between one and eight months.

Disseminated Melioidosis Presenting as Sepsis, Neurological Melioidosis, Liver and Prostate Abscess in United Arab Emirates.

Melioidosis is an infection caused by Burkholderia pseudomallei, a Gram-negative bacterium. It is a disease endemic to Southeast Asia and northern Australia although its global incidence has been rising. It most commonly infects people with certain identified risk factors such as diabetes, alcoholism, thalassemia, and underlying chronic disease involving lungs, kidney and liver. This bacterium is capable of producing a wide array of clinical manifestations ranging from asymptomatic disease to localised infections such as in the lung, bone or skin to disseminated infection. This is a case, from United Arab Emirates, of a 40-year-old male recently diagnosed with diabetes who presented with multiple abscesses and was eventually diagnosed with disseminated melioidosis. He was treated successfully with antibiotics and drainage of abscesses. In non-endemic regions, melioidosis can be easily missed in common diagnostic approaches. This gap of awareness could delay the diagnosis and allow further deterioration of the patient due to complications. Thus, case reports like this can enlighten internists about changing incidences and complexity of clinical presentations, thus preparing them to better handle such patients in the future. Owing to its considerably rare incidence in non-endemic regions including the United Arab Emirates, melioidosis can easily be overlooked or misdiagnosed.Moreover, due to similarity with multiple other diseases and infections as well as significant absence from standard medical curricula, melioidosis is rarely on the differential list of an internist.This report aims to enhance awareness and alertness to aid earlier detection and avoid severe complications.

In Vitro Roles of Burkholderia Intracellular Motility A (BimA) in Infection of Human Neuroblastoma Cell Line.

The bacterial pathogen Burkholderia pseudomallei causes human melioidosis, which can infect the brain, leading to encephalitis and brain abscesses. Infection of the nervous system is a rare condition but is associated with an increased risk of mortality. Burkholderia intracellular motility A (BimA) was reported to play an important role in the invasion and infection of the central nervous system in a mouse model. Thus, to gain insight of the cellular mechanisms underlying the pathogenesis of neurological melioidosis, we explored the human neuronal proteomics to identify the host factors that are up- and downregulated during Burkholderia infection. When infected the SH-SY5Y cells with B. pseudomallei K96243 wild-type (WT), 194 host proteins showed a fold change of >2 compared with uninfected cells. Moreover, 123 proteins showed a fold change of >2 when infected with a knockout bimA mutant (ΔbimA) mutant compared with WT. The differentially expressed proteins were mainly associated with metabolic pathways and pathways linked to human diseases. Importantly, we observed the downregulation of proteins in the apoptosis and cytotoxicity pathway, and in vitro investigation with the ΔbimA mutant revealed the association of BimA with the induction of these pathways. Additionally, we disclosed that BimA was not required for invasion into the neuron cell line but was necessary for effective intracellular replication and multinucleated giant cell (MNGC) formation. These findings show the extraordinary capacity of B. pseudomallei in subverting and interfering with host cellular systems to establish infection and extend our understanding of B. pseudomallei BimA involvement in the pathogenesis of neurological melioidosis. IMPORTANCE Neurological melioidosis, caused by Burkholderia pseudomallei, can result in severe neurological damage and enhance the mortality rate of melioidosis patients. We investigate the involvement of the virulent factor BimA, which mediates actin-based motility, in the intracellular infection of neuroblastoma SH-SY5Y cells. Using proteomics-based analysis, we provide a list of host factors exploited by B. pseudomallei. The expression level of selected downregulated proteins in neuron cells infected with the ΔbimA mutant was determined by quantitative reverse transcription-PCR and was consistent with our proteomic data. The role of BimA in the apoptosis and cytotoxicity of SH-SY5Y cells infected by B. pseudomallei was uncovered in this study. Additionally, our research demonstrates that BimA is required for successful intracellular survival and cell fusion upon infection of neuron cells. Our findings have significant implications for understanding the pathogenesis of B. pseudomallei infections and developing novel therapeutic strategies to combat this deadly disease.

Cycle-Inhibiting Factor Is Associated with Burkholderia pseudomallei Invasion in Human Neuronal Cells.

Simple SummaryNeurological melioidosis, caused by Burkholderia pseudomallei, can lead to the development of severe symptoms associated with the nervous system. However, the pathogenic mechanism through which this bacterium infects neuronal cells has not been studied. This study showed that B. pseudomallei can infect human neuronal SH-SY5Y cells in vitro. Cycle-inhibiting factor (Cif), a type III secreted effector, is one of the virulence factors produced by B. pseudomallei upon infection. The B. pseudomallei cif-deleted mutant reduced the ability to invade neuronal cells compared with the parental strain. Our finding indicates that Cif is associated with B. pseudomallei invasion of human neuronal cells.Burkholderia pseudomallei is a pathogenic bacterium that causes human melioidosis, which is associated with a high mortality rate. However, the underlying mechanisms of B. pseudomallei pathogenesis are largely unknown. In this study, we examined the infection of human neuronal SH-Sy5y cells by several clinically relevant B. pseudomallei strains. We found that all tested B. pseudomallei strains can invade SH-Sy5y cells, undergo intracellular replication, cause actin-tail formation, and form multinucleated giant cells. Additionally, a deletion mutant of B. pseudomallei cycle-inhibiting factor (cif) was constructed that exhibited reduced invasion in SH-Sy5y cells. Complementation of cif restored invasion of the B. pseudomallei cif-deleted mutant. Our findings enhance understanding of B. pseudomallei pathogenicity in terms of the virulence factor Cif and demonstrate the function of Cif in neurological melioidosis. This may eventually lead to the discovery of novel targets for treatment and a strategy to control the disease.

Melioidosis in Critical Care: A Review.

Key Points(1) Diabetes, hazardous alcohol use, and/or significant heart disease are more likely to develop a critical illness with melioidosis. (2) Pneumonia is the most common presentation. Those with pneumonia or bacteremia are most likely to require intensive care unit admissions. (3) Culture is the mainstay for the diagnosis. However, it is noted that Burkholderia pseudomallei is often wrongly identified as Pseudomonas or other Burkholderia species by commonly available commercial techniques. (4) Therapy consists of an intensive phase with intravenous antibiotics to prevent mortality followed by an eradication phase with oral antibiotics to prevent relapse. (5) Meropenem is the drug of choice for those with septic shock or neurological involvement. For patients with nonpulmonary organ focal sites of infection (neurologic, prostatic, bone, joint, cutaneous, and soft tissue melioidosis), the addition of trimethoprim-sulfamethoxazole (TMP-SMX) to ceftazidime/carbapenem during intensive therapy is recommended. TMP-SMX is the drug of choice for oral antibiotic therapy during the eradication phase. (6) Adequate source control is essential for successful treatment and to prevent relapse. (7) The use of granulocyte-colony stimulating factor (G-CSF) those with septic shock is controversial.How to cite this articleSridharan S, B Princess I, Ramakrishnan N. Melioidosis in Critical Care: A Review. Indian J Crit Care Med 2021; 25(Suppl 2):S161–S165.

Neurological melioidosis complicated by cerebral venous sinus thrombosis

Melioidosis is a systemic disease endemic in Southeast Asia and Northern Australia. The spectrum of the disease varies from asymptomatic infection to severe systemic manifestations. Timely diagnosis and treatment of melioidosis is a challenge due to its atypical presentations. We report a case of melioidosis causing cerebral abscesses and cerebral venous sinus thrombosis. Occurrence of these neurological manifestations in melioidosis is rare and it is a difficult condition to diagnose and treat. Timely diagnosis was a challenge in this patient due to the atypical presentation and the use of empirical antibiotics in the primary care setting. Limited laboratory diagnostic capability also contributed to this delay.

Distinct Pathogenic Patterns of Burkholderia pseudomallei Isolates Selected from Caenorhabditis elegans and Dictyostelium discoideum Models.

Burkholderia pseudomallei is a selective agent that causes septic melioidosis and exhibits a broad range of lethal doses in animals. Host cellular virulence and phagocytic resistance are pathologic keys of B. pseudomallei. We first proposed Caenorhabditis elegans as the host cellular virulence model to mimic bacterial virulence against mammals and second established the resistance of B. pseudomallei to predation by Dictyostelium discoideum as the phagocytosis model. The saprophytic sepsis-causing Burkholderia sp. (B. pseudomallei, Burkholderia thailandensis, Burkholderia cenocepacia, and Burkholderia multivorans) exhibited different virulence patterns in both simple models, but B. pseudomallei was the most toxic. Using both models, attenuated isolates of B. pseudomallei were selected from a transposon-mutant library and a panel of environmental isolates and reconfirmed by in vitro mouse peritoneal exudate cell association and invasion assays. The distinct pathological patterns of melioidosis were inducted by different selected B. pseudomallei isolates. Fatal melioidosis was induced by the isolates with high virulence in both simple models within 4-5 day, whereas the low-virulence isolates resulted in prolonged survival greater than 30 day. Infection with the isolates having high resistance to D. discoideum predation but a low C. elegans killing effect led to 83% of mice with neurologic melioidosis. By contrast, infection with the isolates having low resistance to D. discoideum predation but high C. elegans killing effect led to 20% cases with inflammation in the salivary glands. Our results indicated that individual B. pseudomallei isolates selected from simple biological models contribute differently to disease progression and/or tissue tropism.

Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia

Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis, lipopolysaccharide (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to test whether the Trojan horse-like mechanism occurs during endotoxemia. The expression levels of cerebral cytokines, chemokines and cell adhesion molecules; the activation of astrocytes, microglia and endothelial cells; and the increased vascular permeability and brain-infiltrating leukocytes were evaluated using B. pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced brains. Accordingly, different degrees of BBB damage in those brains with endotoxemia were established. The B. multivorans LPS-induced brain exhibited the highest levels of disruptive BBB according to the above mediators/indicators. Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells or free B. pseudomallei were adoptively transferred at equal bacterial concentrations (103 CFU). The bacterial load and number of cases of meningeal neutrophil infiltration in the brains of animals treated with B. pseudomallei-loaded Ly6C cells were higher than those in brains induced by free B. pseudomallei in any of the endotoxemic groups. In particular, these results were reproducible in B. multivorans LPS-induced brains. We suggest that B. pseudomallei-loaded cells can act as a Trojan horse and are more effective than free B. pseudomallei in invading the CNS under septic or endotoxemic conditions even when there is a high degree of BBB disruption.

Melioidosis in India and Bangladesh: A review of case reports

Objective: To conduct an epidemiological and clinical review of published case reports of melioidosis from India and Bangladesh. Methods: Data from published case reports were abstracted and summarized. We further compared the clinical epidemiology of the melioidosis cases in India with case series from highly endemic areas in Northern Australia and Southeast Asia to elucidate any differences in presentations and risk factors between the regions. Results: We identified a total of 99 cases published between 1953 and June 2016, originating from India (n=85) or Bangladesh (n=14). Cases were predominantly male and ranged in age from 1 month to 90 years. Diabetes mellitus was the most common risk factor reported (58%). About 28% of the cases had history of exposure via high-risk occupations or exposure to contaminated water. The overall case fatality rate (CFR) was 26%. Factors influencing mortality included the occurrence of septic shock (CFR, 80%), environmental exposure (CFR, 39%), primary presentation of pneumonia (CFR, 38%), misdiagnosed and/or mistreated cases (CFR, 33%) or the presence of a risk factor (CFR, 29%). Because of the small number of cases in Bangladesh, pattern of clinical epidemiology is limited to India. Soft tissue abscess (37%) was the most common clinical presentation reported from India followed by pneumonia (24%) and osteomyelitis/septic arthritis (18%). Neurological melioidosis (n=10, 12%) presented as pyemic lesions of the brain or meninges. A few cases of prostatic abscess (n=4) in men and parotid abscess (n=4) were also noted. The above patterns were consistent with case series from Southeast Asia and Northern Australia for the most part, in terms of risk factors associated with infection and factors influencing mortality. Differences included clinical presentation of pneumonia which was notably lower than that reported in Southeast Asia and Northern Australia; a higher proportion of neurological and parotid abscess presentation; and a lower CFR compared to that reported in case series in Southeast Asia. About 39% of the cases were misdiagnosed and/or mistreated, suggesting underreporting and under estimation of the true disease burden. Conclusions: The concentration of melioidosis cases in southern and eastern states in India and in Bangladesh, which share climatic conditions and rice farming activities with known endemic areas in Southeast Asia, suggests an endemicity of melioidosis in this region. Thus, increased awareness among healthcare personnel, particularly among clinicians and nurses practicing in rural areas, and improved surveillance through case registries is essential to guide early diagnosis and prompt treatment.

The epidemiology and clinical manifestation of neurological melioidosis: A series of 19 cases from Southwest India over 10 years

The epidemiology and clinical manifestation of neurological melioidosis: A series of 19 cases from Southwest India over 10 years

Increased Neurotropic Threat from Burkholderia pseudomallei Strains with a B. mallei-like Variation in the bimA Motility Gene, Australia.

Neurologic melioidosis is a serious, potentially fatal form of Burkholderia pseudomallei infection. Recently, we reported that a subset of clinical isolates of B. pseudomallei from Australia have heightened virulence and potential for dissemination to the central nervous system. In this study, we demonstrate that this subset has a B. mallei-like sequence variation of the actin-based motility gene, bimA. Compared with B. pseudomallei isolates having typical bimA alleles, isolates that contain the B. mallei-like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health.

Central nervous system melioidosis in the pediatric age group: review

Melioidosis is a potentially fatal infectious disease caused by Burkholderia pseudomallei. Neurologic involvement in pediatric age group is very rare, and only a handful of cases have been reported in literature. We sought to provide a systematic review of pediatric neurologic melioidosis. Literature review was performed to analyze reported cases of pediatric neurologic melioidosis (≤16years) by searching online database (PubMed/MEDLINE). Twenty-seven cases were analyzed. Mean age was 6.7years (range 2days-14years) and around 50% were older children (>5years). Cranial nerve palsies and fever were most common presenting features. Major manifestations were meningoencephalitis in 16 (59%) and cerebral abscesses in eight (29%) cases. Abscesses were mostly located in parietal lobe. Among older children, abscesses were common than meningeal disease, while being converse for neonates. Mean follow-up duration was 11.5months. Ten cases showed good to excellent outcome, while eight cases had fair (incomplete recovery) outcomes. The overall mortality rate was 18.5% (5/27) and tends to decrease with age. Among the five deaths, 4 (80%) had septicemia or pneumonia. Pediatric neurologic melioidosis is very rare. Meningoencephalitis is the most common presentation. Mortality is the highest in neonates. Ceftazidime appears to be the drug of choice in intensive phase, although the best drug in maintenance phase cannot be commented upon, especially in very young children.

A fatal case of melioidosis with pancytopenia in a traveler from Indonesia

Melioidosis, an infectious disease with high mortality, caused by Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. In Indonesia, autochthonous cases have been rarely reported, with most cases being sporadic and occurring in travelers. Herein, we report a fatal case of neurological melioidosis in a traveler from Indonesia presenting with septic shock.

Involvement of L-selectin expression in Burkholderia pseudomallei-infected monocytes invading the brain during murine melioidosis

ABSTRACTThe development of neurologic melioidosis was linked to the elicitation of Burkholderia pseudomallei-infected L-selectinhiCD11b+ BALB/c cells in our previous study. However, whether monocytic L-selectin (CD62L, encoded by the sell gene) is a key factor remains uncertain. In the present study, after establishing multi-organ foci via hematogenous routes, we demonstrated that B. pseudomallei GFP steadily persisted in blood, splenic, hepatic and bone marrow (BM) Ly6C monocytes; however, the circulating CD16/32+CD45hiGFP+ brain-infiltrating leukocytes (BILs) derived from the blood Ly6C monocytes were expanded in BALB/c but not in C57BL/6 bacteremic melioidosis. Consistent with these results, 60% of BALB/c mice but only 10% of C57BL/6 mice exhibited neurologic melioidosis. In a time-dependent manner, B. pseudomallei invaded C57BL/6 BM-derived phagocytes and monocytic progenitors by 2 d. The number of Ly6C+CD62L+GFP+ inflamed cells that had expanded in the BM and that were ready for emigration peaked on d 21 post-infection. Hematogenous B. pseudomallei-loaded sell+/+Ly6C monocytes exacerbated the bacterial loads and the proportion of Ly6C+GFP+ BILs in the recipient brains compared to sell-/- infected Ly6C cells when adoptively transferred. Moreover, a neutralizing anti-CD62L antibody significantly depleted the bacterial colonization of the brain following adoptive transfer of B. pseudomallei-loaded C57BL/6 or BALB/c Ly6C cells. Our data thus suggest that Ly6C+CD62L+ infected monocytes served as a Trojan horse across the cerebral endothelium to induce brain infection. Therefore, CD62L should be considered as not only a temporally elicited antigen but also a disease-relevant leukocyte marker during the development of neurologic melioidosis.

Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation.

Infection with Burkholderia pseudomallei causes melioidosis, a disease with a high mortality rate (20% in Australia and 40% in Southeast Asia). Neurological melioidosis is particularly prevalent in northern Australian patients and involves brain stem infection, which can progress to the spinal cord; however, the route by which the bacteria invade the central nervous system (CNS) is unknown. We have previously demonstrated that B. pseudomallei can infect the olfactory and trigeminal nerves within the nasal cavity following intranasal inoculation. As the trigeminal nerve projects into the brain stem, we investigated whether the bacteria could continue along this nerve to penetrate the CNS. After intranasal inoculation of mice, B. pseudomallei caused low-level localized infection within the nasal cavity epithelium, prior to invasion of the trigeminal nerve in small numbers. B. pseudomallei rapidly invaded the trigeminal nerve and crossed the astrocytic barrier to enter the brain stem within 24 h and then rapidly progressed over 2,000 μm into the spinal cord. To rule out that the bacteria used a hematogenous route, we used a capsule-deficient mutant of B. pseudomallei that does not survive in the blood and found that it also entered the CNS via the trigeminal nerve. This suggests that the primary route of entry is via the nerves that innervate the nasal cavity. We found that actin-mediated motility could facilitate initial infection of the olfactory epithelium. Thus, we have demonstrated that B. pseudomallei can rapidly infect the brain and spinal cord via the trigeminal nerve branches that innervate the nasal cavity.

Paediatric neurological melioidosis: a rehabilitation case report

Melioidosis is a rare condition, endemic to northern Australia and south-east Asia, caused by an infection from the bacteria <i>Burkholderia pseudomallei</i>. The largest epidemiological review to date describes 540 cases of melioidosis seen at Darwin Hospital, in northern Australia, over a 20-year period. Of these, 14 (less than 3%) presented with neurological manifestation, with three deaths. Reports of paediatric cases of melioidosis are rarer. In a review of paediatric cases in northern Australia only eight cases were identified in 10 years. Three of these patients presented with neurological melioidosis, of whom two died in hospital. Whilst the literature refers to prolonged periods of hospitalisation for survivors, the trajectory of functional recovery and process of rehabilitation has not been described. This is a case report describing a 14-year-old boy who presented to a remote medical post with acute neurological symptoms (vomiting, severe headache, ataxia, cranial nerve VI and VII palsy) and was referred to the tertiary paediatric hospital in Perth, Western Australia. Cranial magnetic resonance imaging showed an extensive infiltrative lesion in the posterior fossa and hydrocephalus. Diagnosis of neurological melioidosis required isolation of the pathogen by brain biopsy through sub-occipital craniotomy. Medical treatment included surgical management of hydrocephalus, parenteral antibiotic treatment with meropenem and then a prolonged course of oral co-trimoxazole, enteral feeding and tonal management with levodopa-carbidopa and botulinum toxin A injections. Associated neurological signs and symptoms (bradykinesia, tremor, dysphagia, aphasia, hypertonia, exotropia) required intensive rehabilitation to address functional deficits and to promote independence. The purpose of this case report is to document the functional recovery and rehabilitation process of a paediatric case of neurological melioidosis. Knowledge of the recovery pathway is important to add to the understanding of natural history and treatment of this rare disease. Occasions of service and functional assessments were recorded prospectively. Inpatient therapy (932 hours, with 934 occasions of service) was delivered across physiotherapy, occupational therapy and speech pathology over 9 months of an inpatient admission. Initial paediatric functional independence measure (WeeFIM) was 18/126, indicating complete dependence in all physical and cognitive domains. Following 9 months of intensive rehabilitation the WeeFIM was 53/126, indicating significant residual disability. This proved to be a challenge for discharge planning back to a remote region of Western Australia. Paediatric neurological melioidosis can lead to significant disability and long-term dependence, despite the provision of lengthy intensive rehabilitation. This case report highlights the challenges and complexity of the rehabilitation services required to optimise outcomes for this patient and achieve a safe discharge to a remote community where limited support services are available.

Neurotropic threat characterization of Burkholderia pseudomallei strains.

The death rate for neurologic melioidosis is high. Whether certain Burkholderia pseudomallei strains are more likely than other strains to cause central nervous system infection and whether route of infection influences the neurotropic threat remain unclear. Therefore, we compared the virulence and dissemination of Australian clinical isolates collected during October 1989-October 2012 from patients with neurologic and nonneurologic melioidosis after intranasal and subcutaneous infection of mice in an experimental model. We did not observe neurotropism as a unique characteristic of isolates from patients with neurologic melioidosis. Rather, a distinct subset of B. pseudomallei strains appear to have heightened pathogenic potential for rapid dissemination to multiple tissues, including the central nervous system, irrespective of the infection route. This finding has valuable public health ramifications for initiating appropriate and timely therapy after exposure to systemically invasive B. pseudomallei strains. Increasing understanding of B. pseudomallei pathology and its influencing factors will further reduce illness and death from this disease.

Melioidosis and end-stage renal disease in tropical northern Australia.

Melioidosis, an infection caused by the Gram-negative bacillus Burkholderia pseudomallei, is endemic in Southeast Asia and northern Australia.1 Presentations include disseminated sepsis with multiorgan abscesses, pneumonia, genitourinary infection, skin and soft tissue infection, osteomyelitis/septic arthritis, and neurological melioidosis. It can be acute or chronic and localized or systemic.

Neurologic Melioidosis

Melioidosis is an important cause of morbidity and mortality in northern Australia and Southeast Asia. Diagnosis is best made by isolation of Burkholderia pseudomallei from clinical specimens. A variety of clinical presentations are described, including neurologic disease. The aim of this study was to review admissions with confirmed neurologic melioidosis to a regional hospital in a region to which melioidosis is endemic during 1995-2011. There were 12 culture-confirmed cases of neurologic melioidosis, of which two were detected by analysis of cerebrospinal fluid. Four of these cases were in children. Significant clinical features were fever, headache, and ataxia. Common changes on magnetic resonance imaging T2-weighted scans included ring-enhancing lesions and leptomeningeal enhancement. There were four deaths and an additional four patients had significant long-term neurologic sequelae. When considering the etiology of undifferentiated neurologic disease, an awareness of the possibility of neurologic melioidosis is important in disease-endemic regions.

Induction of Mouse Melioidosis with Meningitis by CD11b+ Phagocytic Cells Harboring Intracellular B. pseudomallei as a Trojan Horse

BackgroundApproximately 3–5% of patients with melioidosis manifest CNS symptoms; however, the clinical data regarding neurological melioidosis are limited.Methods and FindingsWe established a mouse model of melioidosis with meningitis characterized by neutrophil infiltration into the meninges histologically and B. pseudomallei in the cerebrospinal fluid (CSF) by bacteriological culturing methods. As the disease progresses, the bacteria successively colonize the spleen, liver, bone marrow (BM) and brain and invade splenic and BM cells by days 2 and 6 post-infection, respectively. The predominant cell types intracellularly infected with B. pseudomallei were splenic and BM CD11b+ populations. The CD11b+Ly6Chigh inflamed monocytes, CD11b+Ly6Clow resident monocytes, CD11b+Ly6G+ neutrophils, CD11b+F4/80+ macrophages and CD11b+CD19+ B cells were expanded in the spleen and BM during the progression of melioidosis. After adoptive transfer of CD11b populations harboring B. pseudomallei, the infected CD11b+ cells induced bacterial colonization in the brain, whereas CD11b− cells only partially induced colonization; extracellular (free) B. pseudomallei were unable to colonize the brain. CD62L (selectin) was absent on splenic CD11b+ cells on day 4 but was expressed on day 10 post-infection. Adoptive transfer of CD11b+ cells expressing CD62L (harvested on day 10 post-infection) resulted in meningitis in the recipients, but transfer of CD11b+ CD62L-negative cells did not.Conclusions/SignificanceWe suggest that B. pseudomallei-infected CD11b+ selectin-expressing cells act as a Trojan horse and are able to transmigrate across endothelial cells, resulting in melioidosis with meningitis.