Treatment and prophylaxis of melioidosis

Dance, David A. B.

doi:10.1016/j.ijantimicag.2014.01.005

Cited by 245 publications

(277 citation statements)

References 96 publications

(108 reference statements)

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“…One of the difficulties in treatment is the high level of antibiotic resistance in B. pseudomallei. Trimethoprim and sulfamethoxazole are two of the few clinically useful antibiotics (35). Both of these antibiotics activate malleilactone production in B. thailandensis (Table 1).…”

Section: Discussionmentioning

confidence: 99%

A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone

et al. 2015

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Burkholderia thailandensis has three acyl-homoserine lactone (AHL) LuxR-LuxI quorum-sensing circuits and two orphan LuxR homologs. Orphans are LuxR-type transcription factors that do not have cognate LuxI-type AHL synthases. One of the orphans, MalR, is genetically linked to the mal gene cluster, which encodes enzymes required for production of the cytotoxic polyketide malleilactone. Under normal laboratory conditions the mal gene cluster is silent; however, antibiotics like trimethoprim induce mal transcription. We show that trimethoprim-dependent induction of the mal genes requires MalR. MalR has all of the conserved amino acid residues characteristic of AHL-responsive LuxR homologs, but in B. thailandensis, MalR activation of malleilactone synthesis genes is not responsive to AHLs. MalR can activate transcription from the mal promoter in E. coli without addition of AHLs or trimethoprim. Expression of malR in B. thailandensis is induced by trimethoprim. Our data indicate that MalR binds to a lux box-like element in the mal promoter and activates transcription of the mal genes in an AHL-independent manner. Antibiotics like trimethoprim appear to activate mal gene expression indirectly by somehow activating malR expression. MalR activation of the mal genes represents an example of a LuxR homolog that is not a receptor for an AHL quorum-sensing signal. Our evidence is consistent with the idea that mal gene activation depends solely on sufficient transcription of the malR gene. A cyl-homoserine lactone (AHL) quorum-sensing systems are widespread among the Proteobacteria. AHLs are generated by members of the LuxI family of AHL synthases. Members of the LuxR protein family serve as cognate AHL-dependent transcription factors. Often, the genes targeted by LuxR family members have an 18-to 20-base inverted repeat in their promoter regions that shows conservation across species. These repeat elements are called lux box-like sequences and serve as binding sites for the transcription factors. Sequence identity in pairwise comparisons of LuxR polypeptides is rather limited (18 to 35%), but there is a conserved N-terminal AHL binding region and a conserved C-terminal DNA binding region where sequence identity is higher and where there are highly conserved residues (see references 1 and 2 for reviews).Burkholderia thailandensis has three pairs of luxI-luxR-type genes called btaI1-btaR1, btaI2-btaR2, and btaI3-btaR3. Each of the luxR homologs is linked to its cognate luxI homolog, as is the case for luxI-luxR-type gene pairs in many other bacteria. This species also has two additional luxR homologs, btaR4 (now called malR [see below]) and btaR5 (3). LuxR family members like MalR and BtaR5 are called orphans (4) or solos (5), because the genes encoding these polypeptides are not associated with a luxI homolog. Relatively few orphans have been characterized. Some orphans, like Pseudomonas aeruginosa QscR or Salmonella enterica serovar Typhimurium SdiA, show complete conservation of all of the invariant residues in the ...

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Section: Discussionmentioning

confidence: 99%

A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone

et al. 2015

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“…Some species of the Burkholderia genus, such as B. pseudomallei, B. mallei, B. thailandensis, B. cepacia, B. cenocepacia, and B. multivorans, are pathogenic to both humans and animals (156)(157)(158)(159). At least two patterns of natural ␤-lactam resistance have been identified in this class of bacteria.…”

Section: Toca P Vulgaris R Aquatilis and S Fonticola)mentioning

confidence: 99%

A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes

Slama²,

et al. 2016

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SUMMARYFor medical biologists, sequencing has become a commonplace technique to support diagnosis. Rapid changes in this field have led to the generation of large amounts of data, which are not always correctly listed in databases. This is particularly true for data concerning class A β-lactamases, a group of key antibiotic resistance enzymes produced by bacteria. Many genomes have been reported to contain putative β-lactamase genes, which can be compared with representative types. We analyzed several hundred amino acid sequences of class A β-lactamase enzymes for phylogenic relationships, the presence of specific residues, and cluster patterns. A clear distinction was first made between dd-peptidases and class A enzymes based on a small number of residues (S70, K73, P107, 130SDN132, G144, E166, 234K/R, 235T/S, and 236G [Ambler numbering]). Other residues clearly separated two main branches, which we named subclasses A1 and A2. Various clusters were identified on the major branch (subclass A1) on the basis of signature residues associated with catalytic properties (e.g., limited-spectrum β-lactamases, extended-spectrum β-lactamases, and carbapenemases). For subclass A2 enzymes (e.g., CfxA, CIA-1, CME-1, PER-1, and VEB-1), 43 conserved residues were characterized, and several significant insertions were detected. This diversity in the amino acid sequences of β-lactamases must be taken into account to ensure that new enzymes are accurately identified. However, with the exception of PER types, this diversity is poorly represented in existing X-ray crystallographic data.

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“…27,28 There are technical difficulties in assessing the susceptibility of B. pseudomallei to co-trimoxazole. 29 More than half (6, 54.55%) of the cases showed cotrimoxazole resistant in vitro. Having the culture reports in hand, the patients were treated accordingly.…”

Section: Discussionmentioning

confidence: 99%

Socio-demographic, Clinical and Laboratory Characteristics of Melioidosis: Four-Year Experience of Managing Consecutive 11 Cases in a Tertiary Care Hospital of Bangladesh

et al. 2017

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Treatment and prophylaxis of melioidosis

Cited by 245 publications

References 96 publications

A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone

A Burkholderia thailandensis Acyl-Homoserine Lactone-Independent Orphan LuxR Homolog That Activates Production of the Cytotoxin Malleilactone

A Structure-Based Classification of Class A β-Lactamases, a Broadly Diverse Family of Enzymes

Socio-demographic, Clinical and Laboratory Characteristics of Melioidosis: Four-Year Experience of Managing Consecutive 11 Cases in a Tertiary Care Hospital of Bangladesh

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