Structure and mechanism of potent bifunctional β-lactam- and homoserine lactone-degrading enzymes from marine microorganisms

Selleck, Christopher; Pedroso, Marcelo Monteiro; Wilson, Liam A.; Krco, Stefan; Knaven, Esmée Gianna; Miraula, Manfredi; Mitić, Nataša; Larrabee, James A.; Brück, Thomas; Clark, Alice M.; Guddat, Luke W.

doi:10.1038/s41598-020-68612-z

Cited by 14 publications

(11 citation statements)

References 65 publications

(127 reference statements)

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“…BJP-1 is a new Subclass B3 metallo-lactamase (MBL) that was discovered in Bradyrhizobium japonicum, a nitrogen-xing bacteria used in agriculture, whose genome was recently sequenced [41,42] . BJP-1 is a chromosomally encoded intrinsic MBLs that may not acquire through horizontal gene transfer [43,44] . In this study, the BJP-1 gene was found in nearly 11% of the assemblies, implying that it was transferred from soil microbiota to humans.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Resistome in Lactobacillus Genomic Sequences From the Human Gut

Moradi

Fathollahi

Halimi

et al. 2022

Preprint

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The gut is a complex environment inhabited by a wide range of bacterial species. Lactobacillus species constitute a significant proportion of this environment, and, due to their mobile genetic elements such as plasmids and transposons, are more likely to acquire and transfer antibiotic resistance genes through horizontal gene transfer (HGT). The current study obtained and analyzed 321 genome assemblies to determine the prevalence of intrinsic and acquired antibiotic resistance genes (ARGs) among Lactobacillus species colonizing the human gastrointestinal tract. A total of four high-frequency resistance genes were identified, including dfra42 (42%), poxtA (17.4%), lmrB (12%), and BJP-1 (7.7%), aside from dfra42, which is an intrinsic resistance gene, the other genes are acquired resistance genes. PoxtA was found in several different species, mainly in L. paracasei, whereas BJP-1 and lmrB were only found in one species, L. rhamnosus. IS5-like elements family transposase flanked 11% and 8% of detected lmrB and BJP-1, respectively, while, a variety of insertion sequences surrounded 22% of identified poxtA. Furthermore, to the best of our knowledge, this is the first report of BJP-1 in lactobacilli that would suggest it has transferred from soil microbiota to humans. According to the “One Health” perspective, early detection of a new reservoir would control the global spread of the antibiotic-resistant bacterial species between the three environments, which include humans, the environment, and animals. Finally, the study's findings may then highlight the possibility of lactobacilli acquiring or transmitting resistance to other species within or outside the human intestine.

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Section: Discussionmentioning

confidence: 99%

Characterization of Resistome in Lactobacillus Genomic Sequences From the Human Gut

Moradi

Fathollahi

Halimi

et al. 2022

Preprint

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“…The MVs of both strains contained a sufficient amount of the enzyme to degrade the antibiotic in the cultivation medium and permit the growth of the ampicillin susceptible E. coli. We postulate that it may be an important mechanism of Pectobacterium success in various habitats as some β-lactamases are able to degrade lactone rings [41,42], and N-acyl homoserine lactones (AHLs) are signalling molecules in the quorum sensing mechanism. The quorum sensing mechanism plays an essential role in Pectobacterium virulence and controls the expression of PCWDEs [8,9].…”

Section: Discussionmentioning

confidence: 99%

Membrane Vesicles of Pectobacterium as an Effective Protein Secretion System

Jońca

Waleron

Czaplewska

et al. 2021

IJMS

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Bacteria of genus Pectobacterium are Gram-negative rods of the family Pectobacteriaceae. They are the causative agent of soft rot diseases of crops and ornamental plants. However, their virulence mechanisms are not yet fully elucidated. Membrane vesicles (MVs) are universally released by bacteria and are believed to play an important role in the pathogenicity and survival of bacteria in the environment. Our study investigates the role of MVs in the virulence of Pectobacterium. The results indicate that the morphology and MVs production depend on growth medium composition. In polygalacturonic acid (PGA) supplemented media, Pectobacterium produces large MVs (100–300 nm) and small vesicles below 100 nm. Proteomic analyses revealed the presence of pectate degrading enzymes in the MVs. The pectate plate test and enzymatic assay proved that those enzymes are active and able to degrade pectates. What is more, the pathogenicity test indicated that the MVs derived from Pectobacterium were able to induce maceration of Zantedeschia sp. leaves. We also show that the MVs of β-lactamase producing strains were able to suppress ampicillin activity and permit the growth of susceptible bacteria. Those findings indicate that the MVs of Pectobacterium play an important role in host-pathogen interactions and niche competition with other bacteria. Our research also sheds some light on the mechanism of MVs production. We demonstrate that the MVs production in Pectobacterium strains, which overexpress a green fluorescence protein (GFP), is higher than in wild-type strains. Moreover, proteomic analysis revealed that the GFP was present in the MVs. Therefore, it is possible that protein sequestration into MVs might not be strictly limited to periplasmic proteins. Our research highlights the importance of MVs production as a mechanism of cargo delivery in Pectobacterium and an effective secretion system.

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“…This similarity challenges the classification of the serine-dependent enzymes and the metal-dependent enzymes found in marine bacteria. When such enzymes are purified and annotated as β-lactamases (and often as having an ancient heritage) [ 148 , 149 , 150 , 151 , 152 ], is the basis for their heritage that of β-lactam resistance or that of quorum quenching [ 153 ]? Selleck et al suggest credibly that lactonase/lactamase promiscuity may offer an evolutionary advantage [ 153 ].…”

Section: Does the Marine Environment Contain β-Lactam-degrading Enzymes?mentioning

confidence: 99%

β-Lactams from the Ocean

Fisher

Mobashery

2023

Marine Drugs

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The title of this essay is as much a question as it is a statement. The discovery of the β-lactam antibiotics—including penicillins, cephalosporins, and carbapenems—as largely (if not exclusively) secondary metabolites of terrestrial fungi and bacteria, transformed modern medicine. The antibiotic β-lactams inactivate essential enzymes of bacterial cell-wall biosynthesis. Moreover, the ability of the β-lactams to function as enzyme inhibitors is of such great medical value, that inhibitors of the enzymes which degrade hydrolytically the β-lactams, the β-lactamases, have equal value. Given this privileged status for the β-lactam ring, it is therefore a disappointment that the exemplification of this ring in marine secondary metabolites is sparse. It may be that biologically active marine β-lactams are there, and simply have yet to be encountered. In this report, we posit a second explanation: that the value of the β-lactam to secure an ecological advantage in the marine environment might be compromised by its close structural similarity to the β-lactones of quorum sensing. The steric and reactivity similarities between the β-lactams and the β-lactones represent an outside-of-the-box opportunity for correlating new structures and new enzyme targets for the discovery of compelling biological activities.

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Structure and mechanism of potent bifunctional β-lactam- and homoserine lactone-degrading enzymes from marine microorganisms

Cited by 14 publications

References 65 publications

Characterization of Resistome in Lactobacillus Genomic Sequences From the Human Gut

Characterization of Resistome in Lactobacillus Genomic Sequences From the Human Gut

Membrane Vesicles of Pectobacterium as an Effective Protein Secretion System

β-Lactams from the Ocean

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