burkholderia pseudomallei
Recently Published Documents





2022 ◽  
Vol 12 (1) ◽  
Mihnea R. Mangalea ◽  
Bradley R. Borlee

AbstractBurkholderia pseudomallei is a saprophytic bacterium endemic throughout the tropics causing severe disease in humans and animals. Environmental signals such as the accumulation of inorganic ions mediates the biofilm forming capabilities and survival of B. pseudomallei. We have previously shown that B. pseudomallei responds to nitrate and nitrite by inhibiting biofilm formation and altering cyclic di-GMP signaling. To better understand the roles of nitrate-sensing in the biofilm inhibitory phenotype of B. pseudomallei, we created in-frame deletions of narX (Bp1026b_I1014) and narL (Bp1026b_I1013), which are adjacent components of a conserved nitrate-sensing two-component system. We observed transcriptional downregulation in key components of the biofilm matrix in response to nitrate and nitrite. Some of the most differentially expressed genes were nonribosomal peptide synthases (NRPS) and/or polyketide synthases (PKS) encoding the proteins for the biosynthesis of bactobolin, malleilactone, and syrbactin, and an uncharacterized cryptic NRPS biosynthetic cluster. RNA expression patterns were reversed in ∆narX and ∆narL mutants, suggesting that nitrate sensing is an important checkpoint for regulating the diverse metabolic changes occurring in the biofilm inhibitory phenotype. Moreover, in a macrophage model of infection, ∆narX and ∆narL mutants were attenuated in intracellular replication, suggesting that nitrate sensing contributes to survival in the host.

Sruthi Vinayan ◽  
U. Pratibha Bhat

Melioidosis is a severe systemic infectious disease caused by Burkholderia pseudomallei, a gram-negative bacillus with bipolar staining. It is an environmental saprophyte endemic to Southeast Asia and Northern Australia. The disease can have varying manifestations. This is a retrospective study of the clinical and microbiological profile of culture-proven cases of melioidosis who presented to a tertiary care hospital in Coastal Karnataka between January 2018 and December 2020. The epidemiological, demographic, clinical and laboratory characteristics were studied and analyzed. A total of 27 cases were seen during the study period. All patients were from the western coastal areas of India. Fever was the most common presenting complaint. Analysis of the clinical manifestations showed 11 (40.74%) with bacteremia. Pneumonia was the most common primary clinical presentation with 11 cases (40.74%). 9 (33.3%) patients had an abscess in some part of the body on presentation. Secondary foci were seen in 5 (18.5%) patients. The prominent risk factors seen were history of type 2 diabetes mellitus, age >40 years, alcoholism and smoking. 13 (48.15%) were started with the treatment regimen for melioidosis. Only 8 (29.63%) were prescribed the eradication treatment regimen. One case which was inadequately treated came back with reactivation of melioidosis. Varied clinical presentation of melioidosis makes the specific clinical diagnosis difficult. Due to the high mortality and morbidity rate, early diagnosis and prompt management is warranted, this requires clinical vigilance and an intensive microbiological workup. Lack of adherence to the treatment protocol can lead to reactivation.

Guillaume A. Petit ◽  
Biswaranjan Mohanty ◽  
Róisín M. McMahon ◽  
Stefan Nebl ◽  
David H. Hilko ◽  

Disulfide-bond-forming proteins (Dsbs) play a crucial role in the pathogenicity of many Gram-negative bacteria. Disulfide-bond-forming protein A (DsbA) catalyzes the formation of the disulfide bonds necessary for the activity and stability of multiple substrate proteins, including many virulence factors. Hence, DsbA is an attractive target for the development of new drugs to combat bacterial infections. Here, two fragments, bromophenoxy propanamide (1) and 4-methoxy-N-phenylbenzenesulfonamide (2), were identified that bind to DsbA from the pathogenic bacterium Burkholderia pseudomallei, the causative agent of melioidosis. The crystal structures of oxidized B. pseudomallei DsbA (termed BpsDsbA) co-crystallized with 1 or 2 show that both fragments bind to a hydrophobic pocket that is formed by a change in the side-chain orientation of Tyr110. This conformational change opens a `cryptic' pocket that is not evident in the apoprotein structure. This binding location was supported by 2D-NMR studies, which identified a chemical shift perturbation of the Tyr110 backbone amide resonance of more than 0.05 p.p.m. upon the addition of 2 mM fragment 1 and of more than 0.04 p.p.m. upon the addition of 1 mM fragment 2. Although binding was detected by both X-ray crystallography and NMR, the binding affinity (K d) for both fragments was low (above 2 mM), suggesting weak interactions with BpsDsbA. This conclusion is also supported by the crystal structure models, which ascribe partial occupancy to the ligands in the cryptic binding pocket. Small fragments such as 1 and 2 are not expected to have a high energetic binding affinity due to their relatively small surface area and the few functional groups that are available for intermolecular interactions. However, their simplicity makes them ideal for functionalization and optimization. The identification of the binding sites of 1 and 2 to BpsDsbA could provide a starting point for the development of more potent novel antimicrobial compounds that target DsbA and bacterial virulence.

Giacomo Quilici ◽  
Andrea Berardi ◽  
Chantal Fabris ◽  
Michela Ghitti ◽  
Marco Punta ◽  

2021 ◽  
Yuexin Wang ◽  
Bo Shen ◽  
Cai Li ◽  
Haiping Wu ◽  
Yanshuang Wang ◽  

Abstract Burkholderia pseudomallei (B. pseudomallei) can cause melioidosis that is usually fatal. A reliable and rapid detection method is greatly needed for disease surveillance and diagnosis. Herein, an ultrasensitive electrochemiluminescence (ECL) biosensor was constructed for accurate determination of B. pseudomallei coupled with multifunctional Au@Co-MOF@ABEI nanocubes and 3D magnetic walking nanomachine. The synthesized nanocubes could not only immobilize enormous ABEI but exhibit superior peroxidase-like activity to decompose H2O2 to produce plentiful reactive oxygen species (ROSs) that could further react with ABEI, so that the enhanced ECL signals were achieved. Meanwhile, the target-activated walking nanomachine was efficiently driven by Exonuclease III (Exo III) for further improving the sensitivity of the biosensor. As a result, the fabricated ECL biosensor could detect pathogenic gene down to 60.3 aM with a linear range from 100.0 aM to 100.0 pM. Moreover, the biosensing platform successfully achieved the determination of B. pseudomallei down to 9.0 CFU mL−1 in serum samples. This work exhibited an ultrasensitive and specific performance for B. pseudomallei detection, which would become a versatile tool in the early diagnosis and treatment of melioidosis.

J. Vijay ◽  
R. Vedamanickam ◽  
K. Saranya Devi

Melioidosis also termed as Whitmore’s disease is an infectious disease which is caused by bacterium Burkholderia pseudomallei.Southeast Asia and northern Australia are endemic to this diseases which is predominantly transmitted in tropical climates.The coarse of disease involves multiple system involvement most common being lungs and it is mistaken as tuberculosis in many times.the other system involved are musculoskeletal and abscess over internal organs in spleen ,liver.This is a case report of 20 year old male presented with history of fever, swelling over multiple sites of the body, reddish discharge from the swelling, with history of planting trees in the past. Routine investigation showed leucocytosis and multiple abscess in liver and spleen .Blood culture showed positive for burkholderia pseudomallei .started treatment with meropenam and linezolid for 2 weeks and patient resolved from symptoms completely and discharged. Here we discuss about an clinical coarse and treatment response to bacteria burkholderia pseudomallei.

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261382
Noorfatin Jihan Zulkefli ◽  
Cindy Shuan Ju Teh ◽  
Vanitha Mariappan ◽  
Soo Tein Ngoi ◽  
Jamuna Vadivelu ◽  

Burkholderia pseudomallei (B. pseudomallei) is an intracellular pathogen that causes melioidosis, a life-threatening infection in humans. The bacterium is able to form small colony variants (SCVs) as part of the adaptive features in response to environmental stress. In this study, we characterize the genomic characteristics, antimicrobial resistance (AMR), and metabolic phenotypes of B. pseudomallei SCV and wild type (WT) strains. Whole-genome sequence analysis was performed to characterize the genomic features of two SCVs (CS and OS) and their respective parental WT strains (CB and OB). Phylogenetic relationship between the four draft genomes in this study and 19 publicly available genomes from various countries was determined. The four draft genomes showed a close phylogenetic relationship with other genomes from Southeast Asia. Broth microdilution and phenotype microarray were conducted to determine the AMR profiles and metabolic features (carbon utilization, osmolytes sensitivity, and pH conditions) of all strains. The SCV strains exhibited identical AMR phenotype with their parental WT strains. A limited number of AMR-conferring genes were identified in the B. pseudomallei genomes. The SCVs and their respective parental WT strains generally shared similar carbon-utilization profiles, except for D,L-carnitine (CS), g-hydroxybutyric acid (OS), and succinamic acid (OS) which were utilized by the SCVs only. No difference was observed in the osmolytes sensitivity of all strains. In comparison, WT strains were more resistant to alkaline condition, while SCVs showed variable growth responses at higher acidity. Overall, the genomes of the colony morphology variants of B. pseudomallei were largely identical, and the phenotypic variations observed among the different morphotypes were strain-specific.

2021 ◽  
pp. 19-21
Priyadharshini Swaminathan ◽  
Sankavi SB ◽  
Indumathi K DCP ◽  
Theranirajan Theranirajan

Melioidosis or Whitmore's disease is an infection of humans and animals caused by aerobic gram negative bacillus Burkholderia pseudomallei. This infection with a wide clinical spectrum is predominantly present in tropical climates, mainly Southeast Asia and Northern Australia. The clinical manifestations include pneumonia, skin ulcers or abscesses, osteomyelitis, prostatitis, encephalomyelitis and fulminant septic shock. The denitive diagnosis is made by a positive culture of Burkholderia pseudomallei. The bacteria is innately resistant to 6 classes of commonly used antibiotics. CDC recommends an intensive phase of intravenous antibiotics for 10 to 14 days followed by eradication therapy with oral antibiotics for 3 – 6 months. The intravenous agents effective against the bacteria are meropenem and ceftazidime. Trimethoprim sulfamethoxazole and amoxicillin/clavulanic acid are the oral antimicrobial agents used. Here we present two cases of Melioidosis, at opposite ends of the spectrum with varying antibiotic response. One patient is a young non immunocompromised female and the second an elderly immunocompromised (T2DM) male, both presented with skeletal melioidosis.

2021 ◽  
Grace I Borlee ◽  
Mihnea R. Mangalea ◽  
Kevin H. Martin ◽  
Brooke A. Plumley ◽  
Samuel J. Golon ◽  

The regulation and production of secondary metabolites during biofilm growth of Burkholderia spp. is not well understood. To learn more about the crucial role and regulatory control of cryptic molecules produced during biofilm growth, we disrupted c-di-GMP signaling in Burkholderia pseudomallei, a soil-borne bacterial saprophyte and the etiologic agent of melioidosis. Our approach to these studies combined transcriptional profiling with genetic deletions that targeted key c-di-GMP regulatory components to characterize responses to changes in temperature. Mutational analyses and conditional expression studies of c-di-GMP genes demonstrates their contribution to phenotypes such as biofilm formation, colony morphology, motility, and expression of secondary metabolite biosynthesis when grown as a biofilm at different temperatures. RNA-seq analysis was performed at varying temperatures in a ΔII2523 mutant background that is responsive to temperature alterations resulting in hypo- and hyper- biofilm forming phenotypes. Differential regulation of genes was observed for polysaccharide biosynthesis, secretion systems, and nonribosomal peptide and polyketide synthase (NRPS/PKS) clusters in response to temperature changes. Deletion mutations of biosynthetic gene clusters (BGCs) clusters 2, 11, 14 (syrbactin), and 15 (malleipeptin) in wild-type and ΔII2523 backgrounds also reveals the contribution of these BGCs to biofilm formation and colony morphology in addition to inhibition of Bacillus subtilis and Rhizoctonia solani. Our findings suggest that II2523 impacts the regulation of genes that contribute to biofilm formation and competition. Characterization of cryptic BGCs under differing environmental conditions will allow for a better understanding of the role of secondary metabolites in the context of biofilm formation and microbe-microbe interactions.

Sign in / Sign up

Export Citation Format

Share Document