Discovery and Characterization of New Hydroxamate Siderophores, Baumannoferrin A and B, produced by <i>Acinetobacter baumannii</i>

Penwell, William F.; DeGrace, Nancy; Tentarelli, Sharon; Gauthier, Lise; Gilbert, Catherine; Arivett, Brock A.; Miller, Alita A.; Durand-Réville, Thomas F.; Joubran, Camil; Actis, Luis A.

doi:10.1002/cbic.201500147

Cited by 60 publications

(87 citation statements)

References 48 publications

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“…Siderophore production by a clinical isolate of Acinetobacter calcoaceticus was also reported in the literature . Recently, Actis and co‐workers have identified two new hydroxamate siderophores baumannoferrin A and B from the culture supernatants of Acinetobacter baumannii AYE . To the best of our knowledge, no information is available on the siderophore production by the bacterium A. soli .…”

Section: Introductionmentioning

confidence: 83%

Identification of a New Siderophore Acinetoamonabactin Produced by a Salt‐Tolerant Bacterium Acinetobacter Soli

et al. 2018

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A halotolerant bacterium Acinetobacter soli (MTCC 5918), isolated from the salt farm of our institute, was found to secrete a novel siderophore under iron deprivation conditions. A combination of multinuclear one and two dimensional NMR spectroscopies in conjunction with mass technique revealed that the siderophore, we named acinetoamonabactin (1), is a triscatechol derivative of tris(aminomethyl)methylamine.

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Section: Introductionmentioning

confidence: 83%

Identification of a New Siderophore Acinetoamonabactin Produced by a Salt‐Tolerant Bacterium Acinetobacter Soli

et al. 2018

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“…baumannii ATCC 17978 encodes siderophore biosynthetic systems for acinetobactin (73), baumanoferrin (39), and fimsbactin (40), as well as Fur-regulated (34,35) TBDT for ferric siderophores that it does not synthesize (e.g., FhuA-Fc, FhuE-Ferhodotorulate, and FepA-FeEnt). Hence, A. baumannii ORF A1S_0980-A1S_0980 encodes AbaFepA, the iron-regulated OM receptor for FeEnt, which efficiently transported the catecholate ferric siderophore.…”

Section: Discussionmentioning

confidence: 99%

“…Acinetobactin is a high-affinity, catecholate siderophore and a virulence factor (36)(37)(38) that is nearly ubiquitous among the currently sequenced A. baumannii strains. At least two other siderophore biosynthetic gene clusters exist in A. baumannii (34), one for the hydroxamates baumanoferrin A and B (39) and another for fimsbactin (40). Besides the secretion of these siderophores and uptake of their ferric complexes, A. baumannii produces transporters for iron complexes of other siderophores that it does not produce.…”

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confidence: 99%

Fluorescence High-Throughput Screening for Inhibitors of TonB Action

et al. 2017

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Gram-negative bacteria acquire ferric siderophores through TonBdependent outer membrane transporters (TBDT). By fluorescence spectroscopic hghthroughput screening (FLHTS), we identified inhibitors of TonB-dependent ferric enterobactin (FeEnt) uptake through Escherichia coli FepA (EcoFepA). Among 165 inhibitors found in a primary screen of 17,441 compounds, we evaluated 20 in secondary tests: TonB-dependent ferric siderophore uptake and colicin killing and proton motive force-dependent lactose transport. Six of 20 primary hits inhibited TonBdependent activity in all tests. Comparison of their effects on [ 59 Fe]Ent and [ 14 C]lactose accumulation suggested several as proton ionophores, but two chemicals, ebselen and ST0082990, are likely not proton ionophores and may inhibit TonBExbBD. The facility of FLHTS against E. coli led us to adapt it to Acinetobacter baumannii. We identified its FepA ortholog (AbaFepA), deleted and cloned its structural gene, genetically engineered 8 Cys substitutions in its surface loops, labeled them with fluorescein, and made fluorescence spectroscopic observations of FeEnt uptake in A. baumannii. Several Cys substitutions in AbaFepA (S279C, T562C, and S665C) were readily fluoresceinated and then suitable as sensors of FeEnt transport. As in E. coli, the test monitored TonB-dependent FeEnt uptake by AbaFepA. In microtiter format with A. baumannii, FLHTS produced Z= factors 0.6 to 0.8. These data validated the FLHTS strategy against even distantly related Gram-negative bacterial pathogens. Overall, it discovered agents that block TonB-dependent transport and showed the potential to find compounds that act against Gram-negative CRE (carbapenemresistant Enterobacteriaceae)/ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Our results suggest that hundreds of such chemicals may exist in larger compound libraries.IMPORTANCE Antibiotic resistance in Gram-negative bacteria has spurred efforts to find novel compounds against new targets. The CRE/ESKAPE pathogens are resistant bacteria that include Acinetobacter baumannii, a common cause of ventilator-associated pneumonia and sepsis. We performed fluorescence high-throughput screening (FLHTS) against Escherichia coli to find inhibitors of TonB-dependent iron transport, tested them against A. baumannii, and then adapted the FLHTS technology to allow direct screening against A. baumannii. This methodology is expandable to other drugresistant Gram-negative pathogens. Compounds that block TonB action may interfere with iron acquisition from eukaryotic hosts and thereby constitute bacteriostatic antibiotics that prevent microbial colonization of human and animals. The FLHTS method may identify both species-specific and broad-spectrum agents against Gram-negative bacteria.

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“…Surface-associated motility of the nosocomial ␥-proteobacterial pathogen Acinetobacter baumannii was found to depend on biosynthesis of 1,3diaminopropane, a relatively rare polyamine (92). It is perhaps salient that A. baumannii also uses 1,3-diaminopropane and its biosynthetic precursor 2,4-diaminobutyrate in the synthesis of the iron-scavenging siderophores baumannoferrin A and B (93). Polyamine-dependent surface behaviors among different species are listed in Fig.…”

Section: Roles In Biofilm Development and Other Surface Behaviorsmentioning

confidence: 99%

Polyamine function in archaea and bacteria

Michael

2018

Journal of Biological Chemistry

132

130

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Most of the phylogenetic diversity of life is found in bacteria and archaea, and is reflected in the diverse metabolism and functions of bacterial and archaeal polyamines. The polyamine spermidine was probably present in the last universal common ancestor, and polyamines are known to be necessary for critical physiological functions in bacteria, such as growth, biofilm formation, and other surface behaviors, and production of natural products, such as siderophores. There is also phylogenetic diversity of function, indicated by the role of polyamines in planktonic growth of different species, ranging from absolutely essential to entirely dispensable. However, the cellular molecular mechanisms responsible for polyamine function in bacterial growth are almost entirely unknown. In contrast, the molecular mechanisms of essential polyamine functions in archaea are better understood: covalent modification by polyamines of translation factor aIF5A and the agmatine modification of tRNA Ile . As with bacterial hyperthermophiles, archaeal thermophiles require long-chain and branched polyamines for growth at high temperatures. For bacterial species in which polyamines are essential for growth, it is still unknown whether the molecular mechanisms underpinning polyamine function involve covalent or noncovalent interactions. Understanding the cellular molecular mechanisms of polyamine function in bacterial growth and physiology remains one of the great challenges for future polyamine research. Figure 4. Polyamine dependence of biofilm formation in B. subtilis. WT, B. subtilis NCIB3610; ⌬speA, deletion mutant of arginine decarboxylase; Spd, spermidine; Nspd, norspermidine. Complex colony biofilms were grown on solid MSgg medium. Adapted from Hobley et al. (86).

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Discovery and Characterization of New Hydroxamate Siderophores, Baumannoferrin A and B, produced by Acinetobacter baumannii

Cited by 60 publications

References 48 publications

Identification of a New Siderophore Acinetoamonabactin Produced by a Salt‐Tolerant Bacterium Acinetobacter Soli

Identification of a New Siderophore Acinetoamonabactin Produced by a Salt‐Tolerant Bacterium Acinetobacter Soli

Fluorescence High-Throughput Screening for Inhibitors of TonB Action

Polyamine function in archaea and bacteria

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