Structure and Biosynthesis of Fimsbactins A–F, Siderophores from <i>Acinetobacter baumannii</i> and <i>Acinetobacter baylyi</i>

Proschak, Anna; Lubuta, Patrice; Grün, Peter; Löhr, Frank; Wilharm, Gottfried; Berardinis, Véronique de; Bode, Helge B.

doi:10.1002/cbic.201200764

Cited by 81 publications

(133 citation statements)

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“…More recently, it was reported that the A. baumannii ATCC 17978 strain, which could rely on the production and use of acinetobactin and fimsbactins to grow under free-iron limiting conditions (40), is also susceptible to Ga-PPIX. These observations further demonstrate that the antibacterial activity of Ga-PPIX is independent of the type or number of high-affinity iron chelators produced by a particular isolate.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes

Arivett

Fiester

Ohneck

et al. 2015

Antimicrob Agents Chemother

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A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 g/ml. This concentration significantly reduced bacterial viability, while 40 g/ml killed all cells of the A. baumannii ATCC 19606 T and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606 T and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-g/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606 T or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media. Immediately following the advent of antibiotics as therapeutic agents, resistance to these drugs emerged among pathogenic bacteria. Drug-resistant bacterial strains are selected for immediately after initiation of antibiotic regimens, and as a consequence of continued selective pressure, very few treatment options now exist for infections caused by resistant strains of some pathogens (1, 2). The continuing battle with resistance has led to the initial emergence of pathogens displaying multidrug-resistant (MDR) phenotypes, which has since been followed by the emergence of extremely drug-resistant (XDR) or totally drug-resistant (TDR) strains, an outcome that has recreated the preantibiotic era (3, 4). This crisis has involved major Gram-positive and Gram-negative pathogens, including Enterococcus spp., Staphylococcus aureus, members of the family Enterobacteriaceae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Acinetobacter spp. (4). The emergence of MDR strains of each of these microorganisms has contributed to increased morbidity and mortality among patients, leading to extended lengths of hospital stay and exorbitant health care financial burdens that often go unremitted. Compounding this continuum of resistance evolution and treatment failures is t...

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Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes

Arivett

Fiester

Ohneck

et al. 2015

Antimicrob Agents Chemother

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“…8). 203 Additional A. baumannii strains, as well as the nonpathogenic species A. baylyi , also contain the identical cluster. Six fimsbactin isoforms were identified that share a DHB moiety as well as an oxazoline ring derived from a serine residue.…”

Section: Acinetobacter Baumanniimentioning

confidence: 99%

Nonribosomal peptide synthetase biosynthetic clusters of ESKAPE pathogens

Gulick

2017

Nat. Prod. Rep.

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Overview Natural products are important secondary metabolites produced by bacterial and fungal species that play important roles in cellular growth and signaling, nutrient acquisition, intra- and interspecies communication, and virulence. A subset of natural products is produced by nonribosomal peptide synthetases (NRPSs), a family of large, modular enzymes that function in an assembly line fashion. Because of the pharmaceutical activity of many NRPS products, much effort has gone into the exploration of their biosynthetic pathways and the diverse products they make. Many interesting NRPS pathways have been identified and characterized from both terrestrial and marine bacterial sources. Recently, several NRPS pathways in human commensal bacterial species have been identified that produce molecules with antibiotic activity, suggesting another source of interesting NRPS pathways may be the commensal and pathogenic bacteria that live on the human body. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) have been identified as a significant cause of human bacterial infections that are frequently multidrug resistant. The emerging resistance profile of these organisms has prompted calls from multiple international agencies to identify novel antibacterial targets and develop new approaches to treat infections from ESKAPE pathogens. Each of these species contains several NRPS biosynthetic gene clusters. While some have been well characterized and produce known natural products with important biological roles in microbial physiology, others have yet to be investigated. This review catalogs the NRPS pathways of ESKAPE pathogens. The exploration of novel NRPS products may lead to a better understanding of the chemical communication used by human pathogens and potentially to the discovery of novel therapeutic approaches.

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“…The compositions of bacteria related with iron cycling underwent great changes in different ARs and different stages. In the AR with UV/Cl 2 , at stage I, the relative abundance of nitrate-reducing bacteria (NRB) was 9.9%, and among them, 3.9% NRB were related to redox cycling of iron, such as Hyphomicrobium (3.7%) (Stein et al, 2001), and 6% NRB produced siderophores, including Sphingomonas (Duckworth et al, 2009), Brucella (Roop, 2012), Acinetobacter (Proschak et al, 2013) and Azospirillum (Loaces et al, 2011). The ironrespiring bacteria were 11.7%, predominantly including ironreducing bacteria (IRB) Acidobacterium (10.2%) (Nancucheo and Johnson, 2010) and iron-oxidizing bacteria (IOB) Pedomicrobium (1.3%) (Braun et al, 2009).…”

Section: 5mentioning

confidence: 99%

Characterization of biofilm and corrosion of cast iron pipes in drinking water distribution system with UV/Cl2 disinfection

et al. 2014

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Corrosion DisinfectionWater quality Drinking water distribution system a b s t r a c tThe effect of UV/Cl 2 disinfection on the biofilm and corrosion of cast iron pipes in drinking water distribution system were studied using annular reactors (ARs). Passivation occurred more rapidly in the AR with UV/Cl 2 than in the one with Cl 2 alone, decreasing iron release for higher corrosivity of water. Based on functional gene, pyrosequencing assays and principal component analysis, UV disinfection not only reduced the required initial chlorine dose, but also enhanced denitrifying functional bacteria advantage in the biofilm of corrosion scales. The nitrate-reducing bacteria (NRB) Dechloromonas exhibited the greatest corrosion inhibition by inducing the redox cycling of iron to enhance the precipitation of iron oxides and formation of Fe 3 O 4 in the AR with UV/Cl 2 , while the rhizobia Bradyrhizobium and Rhizobium, and the NRB Sphingomonas, Brucella producing siderophores had weaker corrosion-inhibition effect by capturing iron in the AR with Cl 2 . These results indicated that the microbial redox cycling of iron was possibly responsible for higher corrosion inhibition and lower effect of water LarsoneSkold Index (LI) changes on corrosion. This finding could be applied toward the control of water quality in drinking water distribution systems. ª 2014 Elsevier Ltd. All rights reserved. IntroductionIron and steel pipes have been used in water distribution systems for several centuries throughout the world, and are subjected to corrosion, causing deterioration of potable water quality due to unwanted chemical and biochemical reactions (McNeill and Edwards, 2001; Husband and Boxall, 2011). In the corrosion processes of iron pipes, iron ions were released into distributed water, and can re-precipitate forming corrosion scales, also referred to as tubercles (Gerke et al., 2008). The processes can greatly affect water quality in distribution system, not only by releasing iron oxyhydroxides (red water), but also by reactions with e.g. chlorinated disinfection byproducts (Chun et al., 2005), nitrates (Hansen et al., 1996) or natural organic matter (NOM) (Nawrocki et al., 2010 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.else vier.com/locate /wa tres w a t e r r e s e a r c h 6 0 ( 2 0 1 4 ) 1 7 4 e1 8 1http://dx

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Structure and Biosynthesis of Fimsbactins A–F, Siderophores from Acinetobacter baumannii and Acinetobacter baylyi

Cited by 81 publications

References 26 publications

Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes

Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes

Nonribosomal peptide synthetase biosynthetic clusters of ESKAPE pathogens

Characterization of biofilm and corrosion of cast iron pipes in drinking water distribution system with UV/Cl2 disinfection

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