A Young Diabetic Patient With Sepsis After Gardening

Camargo, Nataly; Casadiego, Giovanna K; Fernandez, Dinno A; Millan, Lina V; Hernandez, Angie K; Vargas, Sandra; Ríos, Rafael; Marin-Osorio, Adriana; Salcedo, Soraya; Rodriguez, Deisy L; Bayuelo-Charris, Ilich V; Arias, César A.; Diaz, Lorena; Reyes, Jinnethe

doi:10.1093/ofid/ofaa159

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…The metabolic versatility and adaptability of B. pseudomallei underscores its success as a ubiquitous tropical saprophyte 17 as well as a human pathogen capable of infecting all tissue types tested 50 . B. pseudomallei is recognized as a potential threat to people who come in contact with contaminated soil from domestic gardens in endemic regions 51 , 52 , and may be linked to anthropogenic sources of nitrate and urea in these gardens 53 , 54 . The present study characterizes the nitrosative stress response in B. pseudomallei as it relates to biofilm inhibition via the nitrate-sensing NarX-NarL two-component regulatory system.…”

Section: Discussionmentioning

confidence: 99%

The NarX-NarL two-component system regulates biofilm formation, natural product biosynthesis, and host-associated survival in Burkholderia pseudomallei

Mangalea

Borlee

2022

Sci Rep

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Burkholderia 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.

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Section: Discussionmentioning

confidence: 99%

The NarX-NarL two-component system regulates biofilm formation, natural product biosynthesis, and host-associated survival in Burkholderia pseudomallei

Mangalea

Borlee

2022

Sci Rep

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“… Case 3 Susceptible – to meropenem, ceftazidime, doxycycline, amoxicillin-clavulanate and co-trimoxazole. Case 2 IV ceftazidime 2g thrice daily for a duration of two weeks, advice to continue doxycycline 100mg twice daily for 3 months Case 3 IV ceftazidime 2g thrice daily and IV meropenem 2g e twice daily combination therapy followed by oral cotrimoxazole at 480mg twice a day for six months Both cases were Lost to follow up Reports from India [ 11 ] Kerala B. pseudomallei Fever with altered sensorium Farmer IV meropenem 1g eight hourly Recovered Reports from worldwide [ 12 ] Colombia B. pseudomallei Fever with chills, rigor and right leg pain Gardner IV meropenem 2g 12 hourly and vancomycin 1g 12 hourly Recovered SSI/wound infection Our case Case 4 Case 5 Chennai B. cepacia B. cenocepacia Right lower limb fracture treated with emergency surgery presented with SSI on 5th post-operative day Multiple open fracture treated with emergency surgery presented with SSI Shopkeeper Field worker Susceptible- ceftazidime, Minocycline, cotrimoxazole, Levofloxacin, Meropenem IV Meropenem 2g twice daily two weeks and to continue oral co-trimoxazole 480mg twice daily for six months. Patient completely recovered after follow-up remained free of infection.…”

Section: Septic Arthritismentioning

confidence: 99%

Are Burkholderia Emerging Pathogens in patients with underlying morbidity: A case series

Kumari,

Banu,

Ramanatha

et al. 2024

Heliyon

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The NarX-NarL two-component system is a global regulator of biofilm formation, natural product biosynthesis, and host-associated survival inBurkholderia pseudomallei

Borlee

Mangalea

2020

Preprint

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In the environment, Burkholderia pseudomallei exists as a saprophyte inhabiting soils and surface waters where denitrification is important for anaerobic respiration. As an opportunistic pathogen, B. pseudomallei transitions from the environment to infect human and animal hosts where respiratory nitrate reduction enables replication in anoxic conditions. We have previously shown that B. pseudomallei responds to nitrate and nitrite in part by inhibiting biofilm formation and altering cyclic di-GMP signaling. Here, we describe the global transcriptomic response to nitrate and nitrite to characterize the nitrosative stress response relative to biofilm inhibition. 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 the conserved nitrate-sensing two-component system. Through differential expression analysis of RNA-seq data, we observed that key components of the biofilm matrix are downregulated in response to nitrate and nitrite. In addition, several gene loci associated with the stringent response, central metabolism dysregulation, antibiotic tolerance, and pathogenicity determinants were significantly altered in their expression. 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, in addition to an uncharacterized cryptic NRPS biosynthetic cluster. We also observed reduced expression of ribosomal structural and biogenesis loci, and gene clusters associated with translation and DNA replication, indicating modulation of growth rate and metabolism under nitrosative stress conditions. The differences in expression observed under nitrosative stress 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 is important for host survival.Author SummaryBurkholderia pseudomallei is a saprophytic bacterium inhabiting soils and surface waters 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. In particular, nitrate metabolism inhibits B. pseudomallei biofilm formation through complex regulatory cascades that relay environmental cues to intracellular second messengers that modulate bacterial physiology. Nitrates are common environmental contaminants derived from artificial fertilizers and byproducts of animal wastes that can be readily reduced by bacteria capable of denitrification. In B. pseudomallei 1026b, biofilm dynamics are in part regulated by a gene pathway involved in nitrate sensing, metabolism, and transport. This study investigated the role of a two-component nitrate sensing system, NarX-NarL, in regulating gene expression, biofilm formation, and cellular invasion. Global gene expression analyses in the wild type, as compared to Δ narX and Δ narL mutant strains with nitrate or nitrite implicate the NarX-NarL system in the regulation of biofilm components as well as B. pseudomallei host-associated survival. This study characterizes a conserved nitrate sensing system that is important in environmental and host-associated contexts and aims to bridge a gap between these two important B. pseudomallei lifestyles.

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A Young Diabetic Patient With Sepsis After Gardening

Abstract: We report a case of soft tissue infection, sepsis, and bacteremia due to Burkholderia pseudomallei (melioidosis) in a diabetic young patient and the genomic characterization of Burkholderia pseudomallei isolate (COL-5428).

Cited by 3 publications

References 11 publications

The NarX-NarL two-component system regulates biofilm formation, natural product biosynthesis, and host-associated survival in Burkholderia pseudomallei

The NarX-NarL two-component system regulates biofilm formation, natural product biosynthesis, and host-associated survival in Burkholderia pseudomallei

Are Burkholderia Emerging Pathogens in patients with underlying morbidity: A case series

The NarX-NarL two-component system is a global regulator of biofilm formation, natural product biosynthesis, and host-associated survival inBurkholderia pseudomallei

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