Trimethoprim/sulfamethoxazole for Acinetobacter spp.: A review of current microbiological and clinical evidence

Falagas, Matthew E.; Vardakas, Konstantinos Z.; Roussos, N.

doi:10.1016/j.ijantimicag.2015.04.002

Cited by 48 publications

(28 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ultimately, both antibiotics functionally and synergistically inhibit the synthesis of folate pathway intermediates, including the essential cofactor THF (Fig. 6), which is why they are used together clinically to treat a wide variety of bacterial infections (15,16). Our results suggest that antibiotics targeting folate biosynthesis affect the expression of Csu pili and that 17978pAB3ϩ resistance to Smx provides protection from the effects of this antibiotic.…”

Section: Resultsmentioning

confidence: 80%

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Moon

Weber

Feldman

2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Acinetobacter baumannii is emerging as a multidrug-resistant nosocomial pathogen of increasing threat to human health worldwide. Pili are important bacterial virulence factors, playing a role in attachment to host cells and biofilm formation. The Csu pilus, which is assembled via the chaperone-usher secretion system, has been studied in A. baumannii ATCC 19606. Here we show that, in opposition to previous reports, the common laboratory strain ATCC 17978 produces Csu pili. We found that, although ATCC 17978 was resistant to sulfamethoxazole (Smx) and trimethoprim (Tmp), subinhibitory concentrations of these antibiotics abolished the expression of Csu and consequently produced a dramatic reduction in biofilm formation by ATCC 17978. Smx and Tmp acted synergistically to inhibit the enzymatic systems involved in the bacterial synthesis of tetrahydrofolate (THF), which is required for the synthesis of nucleotides. The effects of these antibiotics were partially relieved by exogenous THF addition, indicating that Smx and Tmp turn off Csu assembly by inducing folate stress. We propose that, for Acinetobacter, nanomolar concentrations of Smx and Tmp represent a "danger signal." In response to this signal, Csu expression is repressed, allowing biofilm dispersal and escape from potentially inhibitory concentrations of antibiotics. The roles of antibiotics as signaling molecules are being increasingly acknowledged, with clear implications for both the treatment of bacterial diseases and the understanding of complex microbial interactions in the environment.KEYWORDS Acinetobacter, folate biosynthesis, folate stress, pilus assembly P ili formed by Gram-negative bacteria play an important role in the ability of these organisms to adhere to surfaces, to form biofilms, and to invade host cells and can affect motility (1). The chaperone-usher (CU) family of pili has been the focus of many studies, and the P-pili and type I pili of uropathogenic Escherichia coli play particularly important roles in establishing infection (2-4). A CU pathway for pilus biogenesis is present in most medically relevant Acinetobacter species (5). The genes for this CU pathway are encoded in a single six-gene operon, termed csu, and include csuA /B, csuA, csuB, csuC, csuD, and csuE (6). In the presence of the CsuC chaperone, CsuA/B polymerizes to form the major pilus subunit (7). Additional experimental and bioinformatic analyses have provided evidence that CsuD functions as the usher and CsuE as a tip adhesin, while CsuA and CsuB may play roles as minor pilin subunits (5,6,8). Despite its being conserved in many sequenced Acinetobacter baumannii strains, the role of Csu has been characterized only for A. baumannii ATCC 19606, an isolate used in many laboratories (5, 6). Genetic studies in this strain have shown that mutation of csuC or

show abstract

Section: Resultsmentioning

confidence: 80%

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Moon

Weber

Feldman

2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Ac . baumannii is an opportunistic pathogen with low virulence which is associated with nosocomial infections and of major concern today because of the emergence of multi-drug resistant isolates 47 . It is unclear why it might be down-regulated in periodontitis relative to health.…”

Section: Resultsmentioning

confidence: 99%

Dysbiosis in chronic periodontitis: Key microbial players and interactions with the human host

Deng

Szafrański

Jarek

et al. 2017

Sci Rep

162

144

View full text Add to dashboard Cite

Periodontitis is an extremely prevalent disease worldwide and is driven by complex dysbiotic microbiota. Here we analyzed the transcriptional activity of the periodontal pocket microbiota from all domains of life as well as the human host in health and chronic periodontitis. Bacteria showed strong enrichment of 18 KEGG functional modules in chronic periodontitis, including bacterial chemotaxis, flagellar assembly, type III secretion system, type III CRISPR-Cas system, and two component system proteins. Upregulation of these functions was driven by the red-complex pathogens and candidate pathogens, e.g. Filifactor alocis, Prevotella intermedia, Fretibacterium fastidiosum and Selenomonas sputigena. Nine virulence factors were strongly up-regulated, among them the arginine deiminase arcA from Porphyromonas gingivalis and Mycoplasma arginini. Viruses and archaea accounted for about 0.1% and 0.22% of total putative mRNA reads, respectively, and a protozoan, Entamoeba gingivalis, was highly enriched in periodontitis. Fourteen human transcripts were enriched in periodontitis, including a gene for a ferric iron binding protein, indicating competition with the microbiota for iron, and genes associated with cancer, namely nucleolar phosphoprotein B23, ankyrin-repeat domain 30B-like protein and beta-enolase. The data provide evidence on the level of gene expression in vivo for the potentially severe impact of the dysbiotic microbiota on human health.

show abstract

“…Notably, carbapenem resistant Acinetobacter species that were SXT-susceptible were noted. Generally, SXT is not very active against Acinetobacter but it was recommended where there are no other options [20], e.g. for infections with pan-resistant strains or in settings where efficacious drugs like carbapenems are expensive [18].…”

Section: Discussionmentioning

confidence: 99%

Genotypic diversity among multidrug resistant Pseudomonas aeruginosa and Acinetobacter species at Mulago Hospital in Kampala, Uganda

et al. 2017

View full text Add to dashboard Cite

BackgroundMultidrug resistant Pseudomonas aeruginosa and Acinetobacter species are common causes of nosocomial infections worldwide. Recently we reported the occurrence of carbapenem resistant Enterobacteriaceae, P. aeruginosa and Acinetobacter species at Mulago National Referral Hospital in Kampala, Uganda, but the isolates were not analyzed for genetic relatedness. Herein we report the intra-species genotypic diversity among P. aeruginosa and Acinetobacter baumannii isolated from hospitalized patients and the environment at Mulago Hospital, using repetitive elements-based PCR (Rep-PCR) genotyping.ResultsA total of 736 specimens from hospitalized patients were processed for culture and sensitivity testing yielding 9 (1.2%) P. aeruginosa and 7 (0.95%) A. baumannii. Similarly, 100 samples from the hospital environment were processed yielding 33 (33%) P. aeruginosa and 13 (13%) A. baumannii. Altogether, 62 non-repetitive isolates were studied (42 P. aeruginosa and 20 A. baumannii), of which 38% (16/42) P. aeruginosa and 40% (8/20) A. baumannii were multidrug resistant (isolates resistant to three or more classes of antimicrobials). Carbapenem resistance prevalence was 33 and 21% for P. aeruginosa from patients and the environment, respectively, while it was 14 and 86% for A. baumannii from patients and environment, respectively. Cluster analysis of the Rep-PCR fingerprints revealed a high level of genetic diversity among the isolates within each species as few isolates were clustered (at 100% level of similarity). More to this, the clustered isolates revealed a complex nature of multidrug resistant P. aeruginosa and A. baumannii clones circulating at Mulago Hospital. Importantly, certain isolates from the environment and patients were clustered, implying that hospitalized patients at Mulago were probably infected with strains from the environment.ConclusionsThe prevalence of multidrug resistant P. aeruginosa and A. baumannii is high at Mulago Hospital but carbapenem resistance prevalence remains relatively low in isolates from hospitalized patients. Importantly, the prevalence of carbapenem resistance in isolates from the environment is high implying the infection control practices at the hospital might be inadequate.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-017-2612-y) contains supplementary material, which is available to authorized users.

show abstract

Trimethoprim/sulfamethoxazole for Acinetobacter spp.: A review of current microbiological and clinical evidence

Cited by 48 publications

References 84 publications

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Dysbiosis in chronic periodontitis: Key microbial players and interactions with the human host

Genotypic diversity among multidrug resistant Pseudomonas aeruginosa and Acinetobacter species at Mulago Hospital in Kampala, Uganda

Contact Info

Product

Resources

About