scholarly journals The Human Microbiome as a Focus of Antibiotic Discovery: Neisseria mucosa Displays Activity Against Neisseria gonorrhoeae

2020 ◽  
Vol 11 ◽  
Author(s):  
Ellen L. Aho ◽  
Jenie M. Ogle ◽  
Anna M. Finck

Neisseria gonorrhoeae infections are a serious global health problem. This organism has developed disturbing levels of antibiotic resistance, resulting in the need for new approaches to prevent and treat gonorrhea. The genus Neisseria also includes several members of the human microbiome that live in close association with an array of microbial partners in a variety of niches. We designed an undergraduate antibiotic discovery project to examine a panel of nonpathogenic Neisseria species for their ability to produce antimicrobial secondary metabolites. Five strains belonging to the N. mucosa species group displayed activity against other Neisseria in delayed antagonism assays; three of these were active against N. gonorrhoeae. The antimicrobial compound secreted by N. mucosa NRL 9300 remained active in the presence of catalase, trypsin, and HEPES buffer, and effectively inhibited a DNA uptake mutant of N. gonorrhoeae. Antimicrobial activity was also retained in an ethyl acetate extract of plate grown N. mucosa NRL 9300. These data suggest N. mucosa produces an antimicrobial secondary metabolite that is distinct from previously described antigonococcal agents. This work also serves as a demonstration project that could easily be adapted to studying other members of the human microbiome in undergraduate settings. We offer the perspective that both introductory and more advanced course-based and apprentice-style antibiotic discovery projects focused on the microbiome have the potential to enrich undergraduate curricula and we describe transferrable techniques and strategies to facilitate project design.

1982 ◽  
Vol 152 (3) ◽  
pp. 1071-1077
Author(s):  
J F Graves ◽  
G D Biswas ◽  
P F Sparling

Piliated, competent gonococci are known to preferentially take up homologous transforming DNA into the cell. We examined the mechanism for DNA uptake with pFA10, a hybrid 11.5-kilobase (kb) penicillin-resistant (Pcr) plasmid composed of heterologous DNA from a 7.2-kb Pcr plasmid and homologous DNA from a 4.2-kb gonococcal cryptic plasmid. The presence of the gonococcal cryptic plasmid DNA in the hybrid resulted in markedly increased transformation efficiencies in isogenic crosses as compared with the parent 7.2-kb Pcr plasmid. Uptake of 32P-end-labeled MspI or TaqI restriction fragments of the hybrid was limited to fragments entirely derived from the 4.2-kb gonococcal cryptic plasmid, indicating that DNA uptake was probably dependent on the presence of a specific DNA sequence. Since Haemophilus DNA did not inhibit transformation by the hybrid Pcr plasmid, the gonococcal DNA uptake sequence is different from the known sequence involved in homologous DNA uptake by Haemophilus spp.


2000 ◽  
Vol 44 (9) ◽  
pp. 2503-2506 ◽  
Author(s):  
Vicki A. Luna ◽  
Sydney Cousin ◽  
William L. H. Whittington ◽  
Marilyn C. Roberts

ABSTRACT The mef gene, originally described for gram-positive organisms and coding for an efflux pump, has been identified in clinical isolates of Acinetobacter junii andNeisseria gonorrhoeae. These strains could transfer themef gene at frequencies ranging from 10−6 to 10−9 into one or more of the following recipients: gram-negative Moraxella catarrhalis, Neisseria perflava/sicca and Neisseria mucosa and gram-positiveEnterococcus faecalis. Three Streptococcus pneumoniae strains could transfer the mef gene intoEikenella corrodens, Haemophilus influenzae,Kingella denitrificans, M. catarrhalis,Neisseria meningitidis, N. perflava/sicca, andN. mucosa at similar frequencies. The mef gene can thus be transferred to and expressed in a variety of gram-negative recipients.


Author(s):  
Saïd Abdellati ◽  
Jolein Laumen ◽  
Natalia Gonzalez ◽  
Sheeba Basil ◽  
Christophe Van Dijck ◽  
...  

We used agar overlay assays to assess if 24 circulating and historical isolates of Neisseria mucosa could inhibit the growth of 28 circulating and historical isolates of N. gonorrhoeae. We found no evidence of inhibition by N. mucosa (n=24). Positive controls Streptococcus pneumoniae and Escherichia coli demonstrated a strong inhibitory effect against the growth of N. gonorrhoeae.


2015 ◽  
Vol 13 (05) ◽  
pp. 1550023 ◽  
Author(s):  
Edgar D. Coelho ◽  
André M. Santiago ◽  
Joel P. Arrais ◽  
José Luís Oliveira

Microbial communities thrive in close association among themselves and with the host, establishing protein–protein interactions (PPIs) with the latter, and thus being able to benefit (positively impact) or disturb (negatively impact) biological events in the host. Despite major collaborative efforts to sequence the Human microbiome, there is still a great lack of understanding their impact. We propose a computational methodology to predict the impact of microbial proteins in human biological events, taking into account the abundance of each microbial protein and its relation to all other microbial and human proteins. This alternative methodology is centered on an improved impact estimation algorithm that integrates PPIs between human and microbial proteins with Reactome pathway data. This methodology was applied to study the impact of 24 microbial phyla over different cellular events, within 10 different human microbiomes. The results obtained confirm findings already described in the literature and explore new ones. We believe the Human microbiome can no longer be ignored as not only is there enough evidence correlating microbiome alterations and disease states, but also the return to healthy states once these alterations are reversed.


2016 ◽  
Vol 198 (18) ◽  
pp. 2515-2523 ◽  
Author(s):  
Christof Hepp ◽  
Heike Gangel ◽  
Katja Henseler ◽  
Niklas Günther ◽  
Berenike Maier

ABSTRACTNeisseria gonorrhoeaeis naturally competent for transformation. The first step of the transformation process is the uptake of DNA from the environment into the cell. This transport step is driven by a powerful molecular machine. Here, we addressed the question whether this machine imports single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) at similar rates. The fluorescence signal associated with the uptake of short DNA fragments labeled with a single fluorescent marker molecule was quantified. We found that ssDNA with a double-stranded DNA uptake sequence (DUS) was taken up with a similar efficiency as dsDNA. Imported ssDNA was degraded rapidly, and the thermonuclease Nuc was required for degradation. In anucdeletion background, dsDNA and ssDNA with a double-stranded DUS were imported and used as the substrates for transformation, whereas the import and transformation efficiencies of ssDNA with single-stranded DUS were below the detection limits. We conclude that the DNA uptake machine requires a double-stranded DUS for efficient DNA recognition and transports ssDNA and dsDNA with comparable efficiencies.IMPORTANCEBacterial transformation enables bacteria to exchange genetic information. It can speed up adaptive evolution and enhances the potential of DNA repair. The transport of DNA through the outer membrane is the first step of transformation in Gram-negative species. It is driven by a powerful molecular machine whose mechanism remains elusive. Here, we show forNeisseria gonorrhoeaethat the machine transports single- and double-stranded DNA at comparable rates, provided that the species-specific DNA uptake sequence is double stranded. Moreover, we found that single-stranded DNA taken up into the periplasm is rapidly degraded by the thermonuclease Nuc. We conclude that the secondary structure of transforming DNA is important for the recognition of self DNA but not for the process of transport through the outer membrane.


1998 ◽  
Vol 180 (19) ◽  
pp. 5117-5122 ◽  
Author(s):  
Michael S. Chaussee ◽  
Stuart A. Hill

ABSTRACT Neisseria gonorrhoeae is naturally competent for DNA transformation. In contrast to other natural prokaryotic DNA transformation systems, single-stranded donor DNA (ssDNA) has not previously been detected during transformation of N. gonorrhoeae. We have reassessed the physical nature of gonococcal transforming DNA by using a sensitive nondenaturing native blotting technique that detects ssDNA. Consistent with previous analyses, we found that the majority of donor DNA remained in the double-stranded form, and only plasmid DNAs that carried the genus-specific DNA uptake sequence were sequestered in a DNase I-resistant state. However, when the DNA was examined under native conditions, S1 nuclease-sensitive ssDNA was identified in all strains tested except for those bacteria that carried the dud-1 mutation. Surprisingly, ssDNA was also found during transformation of N. gonorrhoeae comAmutants, which suggested that ssDNA was initially formed within the periplasm.


Forests ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 42 ◽  
Author(s):  
Eeva Terhonen ◽  
Kathrin Blumenstein ◽  
Andriy Kovalchuk ◽  
Fred O. Asiegbu

Terrestrial plants including forest trees are generally known to live in close association with microbial organisms. The inherent features of this close association can be commensalism, parasitism or mutualism. The term “microbiota” has been used to describe this ecological community of plant-associated pathogenic, mutualistic, endophytic and commensal microorganisms. Many of these microbiota inhabiting forest trees could have a potential impact on the health of, and disease progression in, forest biomes. Comparatively, studies on forest tree microbiomes and their roles in mutualism and disease lag far behind parallel work on crop and human microbiome projects. Very recently, our understanding of plant and tree microbiomes has been enriched due to novel technological advances using metabarcoding, metagenomics, metatranscriptomics and metaproteomics approaches. In addition, the availability of massive DNA databases (e.g., NCBI (USA), EMBL (Europe), DDBJ (Japan), UNITE (Estonia)) as well as powerful computational and bioinformatics tools has helped to facilitate data mining by researchers across diverse disciplines. Available data demonstrate that plant phyllosphere bacterial communities are dominated by members of only a few phyla (Proteobacteria, Actinobacteria, Bacteroidetes). In bulk forest soil, the dominant fungal group is Basidiomycota, whereas Ascomycota is the most prevalent group within plant tissues. The current challenge, however, is how to harness and link the acquired knowledge on microbiomes for translational forest management. Among tree-associated microorganisms, endophytic fungal biota are attracting a lot of attention for their beneficial health- and growth-promoting effects, and were preferentially discussed in this review.


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