Redox-active secondary metabolites act as interspecies modulators of antibiotic resilience

ABSTRACTBacterial opportunistic pathogens make a wide range of secondary metabolites both in the natural environment and when causing infections, yet how these molecules mediate microbial interactions and their consequences for antibiotic treatment are still poorly understood. Here, we explore the role of two redox-active secondary metabolites, pyocyanin and toxoflavin, as interspecies modulators of antibiotic resilience. We find that these molecules dramatically change susceptibility levels of diverse bacteria to clinical antibiotics. Pyocyanin is made by Pseudomonas aeruginosa, while toxoflavin is made by Burkholderia gladioli, organisms that infect cystic fibrosis and other immunocompromised patients. Both molecules alter the susceptibility profile of pathogenic species within the “Burkholderia cepacia complex” to different antibiotics, either antagonizing or potentiating their effects, depending on the drug’s class. Defense responses regulated by the redox-sensitive transcription factor SoxR potentiate the antagonistic effects these metabolites have against fluoroquinolones, and the presence of genes encoding SoxR and the efflux systems it regulates can be used to predict how these metabolites will affect antibiotic susceptibility of different bacteria. Finally, we demonstrate that inclusion of secondary metabolites in standard protocols used to assess antibiotic resistance can dramatically alter the results, motivating the development of new tests for more accurate clinical assessment.

Characterisation of Plant Growth-Promoting Endophytic Bacteria from Sugarcane and Their Antagonistic Activity against Fusarium moniliforme

The use of endophytic bacteria in agriculture provides an effective way of improving crop yield and significantly reducing chemical usage, such as fungicides. This research was conducted to explore endophytic bacteria with plant growth promotion (PGP) and antifungal activities against Fusarium moniliforme AIT01. In this study, we obtained 52 isolates of endophytic bacteria associated with the roots and stems of sugarcane from Nakhon Ratchasima province, Thailand. In vitro antagonistic activity test showed that 14 out of 52 isolates had antagonistic activity against the fungal pathogen F. moniliforme AIT01. These antagonistic endophytic bacteria were identified as belonging to six different species as follows: Nguyenibacter vanlangensis, Acidomonas methanolica, Asaia bogorensis, Tanticharoenia aidae, Burkholderia gladioli and Bacillus altitudinis based on phenotypic characteristics, along with phylogenetic analysis of their 16S rRNA gene sequences. Seven isolates effectively inhibited F. moniliforme AIT01 mycelial growth by up to 40%. The volatile compounds of six isolates reduced the growth of F. moniliforme AIT01 by over 23%. Moreover, riceberry rice seedlings previously treated with B. gladioli CP28 were found to strongly reduce infection with phytopathogen by 80% in comparison to the non-treated control. Furthermore, the isolates also showed relevant PGP features, including ammonia production, zinc and phosphate solubilisation, auxin and siderophore biosynthesis. These results demonstrated that the tested endophytic bacteria could be successfully utilised as a source of PGP and biocontrol agent to manage diseases caused by F. moniliforme.

Activity of imipenem-relebactam against multi-drug and extensively-drug resistant Burkholderia cepacia complex and Burkholderia gladioli

The Burkholderia cepacia complex (Bcc) and Burkholderia gladioli are opportunistic pathogens that most commonly infect persons with cystic fibrosis or compromised immune systems. Members of the Burkholderia genus are intrinsically multidrug resistant (MDR), possessing both a PenA carbapenemase and an AmpC β-lactamase, which renders treatment of infection due to these species problematic. Here, we tested the β-lactam-β-lactamase inhibitor combination, imipenem-relebactam, against a panel of MDR Bcc and B. gladioli . The addition of relebactam to imipenem dramatically lowered the MICs for Bcc and B . gladioli with only 16% of isolates testing susceptible to imipenem vs. 71.3% being susceptible to the imipenem-relebactam combination. While ceftazidime-avibactam remained the most potent combination drug against this panel of Bcc and B. gladioli , imipenem-relebactam was active against 71.4% of the ceftazidime-avibactam-resistant isolates. Relebactam demonstrated potent inactivation of the Burkholderia multivorans PenA1 with a K i app value of 3.2 μM. Timed mass spectrometry revealed that PenA1 formed a very stable adduct with relebactam, without any detectable desulfation up to 24 hours. Based on our results, imipenem-relebactam may represent an alternative salvage therapy for Bcc and B . gladioli infection, especially in cases where the isolates are resistant to ceftazidime-avibactam.

Pan-Genome Analysis Reveals Host-Specific Functional Divergences in Burkholderia gladioli

Burkholderia gladioli has high versatility and adaptability to various ecological niches. Here, we constructed a pan-genome using 14 genome sequences of B. gladioli, which originate from different niches, including gladiolus, rice, humans, and nature. Functional roles of core and niche-associated genomes were investigated by pathway enrichment analyses. Consequently, we inferred the uniquely important role of niche-associated genomes in (1) selenium availability during competition with gladiolus host; (2) aromatic compound degradation in seed-borne and crude oil-accumulated environments, and (3) stress-induced DNA repair system/recombination in the cystic fibrosis-niche. We also identified the conservation of the rhizomide biosynthetic gene cluster in all the B. gladioli strains and the concentrated distribution of this cluster in human isolates. It was confirmed the absence of complete CRISPR/Cas system in both plant and human pathogenic B. gladioli and the presence of the system in B. gladioli living in nature, possibly reflecting the inverse relationship between CRISPR/Cas system and virulence.

Complete Genome Sequence of Burkholderia gladioli Myophage Mana

ABSTRACT Burkholderia gladioli is known to cause respiratory tract infections in cystic fibrosis patients. Here, we describe the annotation of the 38,038-bp genome sequence of Mana, a P2-like phage of B. gladioli. Understanding the genomic characteristics of phages infecting pathogens like B. gladioli can lead to advancements in phage therapy.