Antibiotic Substances Produced by Pseudomonas Aeruginosa

Hays, Edwin E.; Wells, Ibert C.; Katzman, Philip A.; Cain, C.K.; Jacobs, Francis A.; Thayer, Sidney A.; Doisy, Edward A.; Gaby, W. L.; Roberts, Edward; Muir, R. D.; Carroll, C.J.; Jones, Lloyd R.; Wade, Nelson J.

doi:10.1016/s0021-9258(17)41580-8

Cited by 111 publications

(14 citation statements)

References 10 publications

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“…Investigation of the antimicrobial properties of HAQs dates back to 1945, when an "antibiotic metabolite" was described in P. aeruginosa (34). Although the biosynthesis steps and biology of the HAQs in P. aeruginosa have since been studied in detail, much less is known of those in B. thailandensis (21,31,35).…”

Section: Discussionmentioning

confidence: 99%

Burkholderia thailandensis Methylated Hydroxyalkylquinolines: Biosynthesis and Antimicrobial Activity in Cocultures

Klaus

Majerczyk

Moon

et al. 2020

Appl Environ Microbiol

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The bacterium Burkholderia thailandensis produces an arsenal of secondary metabolites that have diverse structures and roles in the ecology of this soil-dwelling bacterium. In co-culture experiments, B. thailandensis strain E264 secretes an antimicrobial that nearly eliminates another soil bacterium, Bacillus subtilis strain 168. To identify the antimicrobial, we used a transposon mutagenesis approach. This screen identified antimicrobial-defective mutants with insertions in the hmqA, hmqC, and hmqF genes involved in biosynthesis of a family of 2-alkyl-4(1H)-quinolones called 4-hydroxy-3-methyl-2-alkenylquinolines (HMAQs), which are closely related to the Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs). Insertions also occurred in the previously uncharacterized gene BTH_II1576 (“hmqL”). Results confirm that BTH_II1576 is involved in generating N-oxide derivatives of HMAQs (HMAQ-NO). Synthetic HMAQ-NO is active against B. subtilis 168, showing ∼50-fold more activity than HMAQ. Both the methyl group and the length of the carbon side chain account for high activity of HMAQ-NO. The results provide new information on the biosynthesis and activities of HMAQs and reveal new insight into how these molecules might be important for the ecology of B. thailandensis. IMPORTANCE The soil bacterium Burkholderia thailandensis produces 2-alkyl-4(1H)-quinolones, mostly methylated 4-hydroxy-alkenylquinolines, a family of relatively unstudied metabolites similar to molecules also synthesized by Pseudomonas aeruginosa. Several of the methylated 4-hydroxy-alkenylquinolines have antimicrobial activity against other species. We show that Bacillus subtilis strain 168 is particularly susceptible to N-oxidated methyl-alkenylquinolines (HMAQ-NO). We confirmed HMAQ-NO biosynthesis requires the previously unstudied protein HmqL. These results provide new information about the biology of 2-alkyl-4(1H)-quinolones, particularly the methylated 4-hydroxy-alkenylquinolines, which are unique to B. thailandensis. This study also has importance for understanding B. thailandensis secondary metabolites and has implications for potential therapeutic development.

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Section: Discussionmentioning

confidence: 99%

Burkholderia thailandensis Methylated Hydroxyalkylquinolines: Biosynthesis and Antimicrobial Activity in Cocultures

Klaus

Majerczyk

Moon

et al. 2020

Appl Environ Microbiol

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“…They obtained mixed results with this drug, which exerted a toxic effect in humans due to phenazines [ 143 ]. Further research demonstrated that some compounds derived from Pseudomonas genus, such as alkyl quinolones, appeared to be the quorum-sensing molecules that display potent antimicrobial activities [ 146 , 147 , 148 , 149 ]. In 1877, the concept of a microbe inhibiting another microbe started with Louis Pasteur and his colleague Jules François Joubert, who discovered that co-cultivated aerobic bacteria inhibited the growth of Bacillus anthracis [ 137 ].…”

Section: History Of Antibioticsmentioning

confidence: 99%

Antibiotic Discovery and Resistance: The Chase and the Race

et al. 2022

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The history of antimicrobial resistance (AMR) evolution and the diversity of the environmental resistome indicate that AMR is an ancient natural phenomenon. Acquired resistance is a public health concern influenced by the anthropogenic use of antibiotics, leading to the selection of resistant genes. Data show that AMR is spreading globally at different rates, outpacing all efforts to mitigate this crisis. The search for new antibiotic classes is one of the key strategies in the fight against AMR. Since the 1980s, newly marketed antibiotics were either modifications or improvements of known molecules. The World Health Organization (WHO) describes the current pipeline as bleak, and warns about the scarcity of new leads. A quantitative and qualitative analysis of the pre-clinical and clinical pipeline indicates that few antibiotics may reach the market in a few years, predominantly not those that fit the innovative requirements to tackle the challenging spread of AMR. Diversity and innovation are the mainstays to cope with the rapid evolution of AMR. The discovery and development of antibiotics must address resistance to old and novel antibiotics. Here, we review the history and challenges of antibiotics discovery and describe different innovative new leads mechanisms expected to replenish the pipeline, while maintaining a promising possibility to shift the chase and the race between the spread of AMR, preserving antibiotic effectiveness, and meeting innovative leads requirements.

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“…The original preparation of quinolone-based antibiotics for patients with Pseudomonas aeruginosa infection was reported by Wells and his coworkers in 1945. 8 Their preliminary studies suggested that four antibiotics, namely Pyo Ib, Pyo Ic, Pyo II, and Pyo III, have structural similarities based on hydrogenation studies and ultraviolet absorption spectroscopic analysis. Building on initial results, Wells later assigned, after elucidation, 2-nonyl-4-quinolinol, 2-heptyl-4-quinolinol, and 2-(D l -nonenyl-)-4-quinolinol to be Pyo Ic, Pyo Ib, and Pyo III, respectively.…”

Section: Biocatalytic Synthesis Of Quinolonesmentioning

confidence: 99%

“…27,28 Multi-modular Enzyme-Catalyzed Condensation and Cyclization In the cultures of bacteria P. aeruginosa, the biosynthesis of quinolones and their analogs was first identified. 8 These derivatives consist of compounds such as 2,4-dihydroxyquinoline (DHQ) (6), 2-heptyl-4-hydroxyquinoline (HHQ) (7), 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO) (8), and Pseudomonas quinolone signal (Pqs) (9). With the use of biochemical approaches accompanied by genetic strategies, PqsD, a condensing enzyme in the Pqs operon, was determined to achieve DHQ formation in vivo through the condensation reaction between the starter and acetyl units.…”

Section: Non-chss As Biocatalystsmentioning

confidence: 99%

Recent Advances in the Catalytic Synthesis of 4-Quinolones

Shen

Wang

Zhang

et al. 2019

Chem

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The 4-quinolones and their analogs are a heterogeneous group of biologically active compounds that have evolved in modern days to provide utilities at the forefront of antibiotic research. They have been used to combat Gram-negative or Gram-positive bacteria, suppress tumor growth, and treat many serious infections. These antimicrobial agents have also been used to promote apoptosis and DNA repair for the treatment of cancer. This review summarizes the experimental progress made in the synthetic development of various catalytic routes to preparing 4-quinolones and their analogs; discusses our current understanding of the reaction mechanisms involving biocatalytic synthesis, general catalytic synthesis, and asymmetric synthesis; and finally presents the future prospects of the emerging field.

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Antibiotic Substances Produced by Pseudomonas Aeruginosa

Cited by 111 publications

References 10 publications

Burkholderia thailandensis Methylated Hydroxyalkylquinolines: Biosynthesis and Antimicrobial Activity in Cocultures

Burkholderia thailandensis Methylated Hydroxyalkylquinolines: Biosynthesis and Antimicrobial Activity in Cocultures

Antibiotic Discovery and Resistance: The Chase and the Race

Recent Advances in the Catalytic Synthesis of 4-Quinolones

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