bluuebunny/crossref_metadata_2025_split huggingface dataset:
MtlD as a therapeutic target for intestinal and systemic bacterial infections
Authors: Schwieters Andrew , Cole Allysa L. , Rego Emily , Gao Chengyu , Kebriaei Razieh , Wysocki Vicki H. , Gunn John S. , Ahmer Brian M. M. 
Published: December 2024

ABSTRACT

The ability to treat infections is threatened by the rapid emergence of antibiotic resistance among pathogenic microbes. Therefore, new antimicrobials are needed. Here we evaluate mannitol-1-phosphate 5-dehydrogenase (MtlD) as a potential new drug target. In many bacteria, mannitol is transported into the cell and phosphorylated by MtlA, the EIICBA component of a phosphoenolpyruvate-dependent sugar phosphotransferase system. MtlD catalyzes the conversion of mannitol-1-phosphate (Mtl-1P) to fructose-6-phosphate, which enters the glycolytic pathway. Mutants lacking
mtlD
are sensitive to mannitol due to accumulation of Mtl-1P. Here, we constructed
mtlD
mutants in four different bacterial species (
Cronobacter sakazakii
,
Pseudomonas aeruginosa,
five serovars of
Salmonella enterica
, and three strains of
Escherichia coli
), confirming and quantifying their mannitol sensitivity. The quantification of mannitol sensitivity
in vitro
was complicated by an inoculum effect and a resumption of growth following mannitol intoxication. The rate of resumption at different mannitol concentrations and cell population densities is fairly constant and reveals what is likely an intoxication processing rate. Provision of mannitol in drinking water, or by intraperitoneal injection, dramatically attenuates infection of a
Salmonella enterica
serovar Typhimurium
mtlD
mutant in mouse models of both gastroenteritis and systemic infection. Using CC003/Unc mice, we find that a
mtlD
mutant of
Salmonella enterica
serovar Typhi is also attenuated by provision of mannitol in drinking water. Therefore, we postulate that MtlD could be a valuable new therapeutic target.

IMPORTANCE

The ability to treat infections is threatened by the rapid emergence of antibiotic resistance. Mannitol is a polyol used in human medicine and the food industry. During catabolism of mannitol, many bacteria transport mannitol across the inner membrane forming the toxic intermediate mannitol-1-phosphate (Mtl-1P). Mtl-1P must be processed by mannitol dehydrogenase (MtlD) or it accumulates intracellularly, causing growth attenuation. We test and confirm here that
mtlD
mutants of
Escherichia coli
(including UPEC, and EHEC),
Salmonella
(including serovars Typhi, and Paratyphi A, B, and C),
Cronobacter
, and
Pseudomonas
experience mannitol sensitivity
in vitro
. Furthermore, providing mannitol in drinking water can alleviate both gastrointestinal and systemic
Salmonella
infections in mice. This suggests that inhibition of MtlD could be a viable antimicrobial strategy.
Short-term evolution and dispersal patterns of fluconazole-resistance in
Candida auris
clade III
Authors: Cancino-Muñoz Irving , Mulet-Bayona Juan Vicente , Salvador-García Carme , Tormo-Palop Nuria , Guna Remedios , Gimeno-Cardona Concepción , González-Candelas Fernando 
Published: December 2024

ABSTRACT

The rapid increase in infections caused by the emerging fungal pathogen
Candida auris
is of global concern, and understanding its expansion is a priority. The phylogenetic diversity of the yeast is clustered in five major clades, among which clade III is particularly relevant, as most of its strains exhibit resistance to fluconazole, reducing the therapeutic alternatives and provoking outbreaks that are difficult to control. In this study, we have investigated the phylogenetic structure of clade III by analyzing a global collection of 566 genomes. We have identified three subgroups within clade III, among which two are genetically most closely related. Moreover, we have estimated the evolutionary rate of clade III to be 2.25e-7 s/s/y (2.87 changes per year). We found that one of these subgroups shows intrinsic resistance to fluconazole and is responsible for the majority of cases within this clade globally. We inferred that this subgroup may have originated around December 2010 (95% High Probability Density (HPD): April 2010–June 2011), and since then it has spread across continents, generating multiple large outbreaks, each with a unique pattern of transmission and dissemination. These results highlight the remarkable ability of the pathogen to adapt to its environment and its rapid global spread, underscoring the urgent need to address this epidemiological challenge effectively.

IMPORTANCE

The number of cases affected by
Candida auris
has increased worryingly worldwide. Among the currently recognized clades, clade III has the highest proportion of fluconazole-resistant cases and is spreading very rapidly, causing large nosocomial outbreaks across the globe. By analyzing complete fungal genomes from around the world, we have confirmed the origin of this clade and unraveled its dispersal patterns in the early 2010s. This finding provides knowledge that may be helpful to the public health authorities for the control of the disease.
Pseudomonas aeruginosa
alkyl quinolone response is dampened by
Enterococcus faecalis
Authors: Fink Maggie M. , Weaver Abigail A. , Parmar Dharmeshkumar , Paczkowski Jon E. , Li Lingyun , Klaers Maggie K. , Junker Ella A. , Jarocki Elizabeth A. , Sweedler Jonathan V. , Shrout Joshua D. 
Published: December 2024

ABSTRACT

The bacterium
Pseudomonas aeruginosa
is an opportunistic pathogen that can cause lung, skin, wound, joint, urinary tract, and eye infections. While
P. aeruginosa
is known to exhibit a robust competitive response toward other bacterial species, this bacterium is frequently identified in polymicrobial infections where multiple species survive. For example, in prosthetic joint infections,
P. aeruginosa
can be identified along with other pathogenic bacteria including
Staphylococcus aureus
,
Enterococcus faecalis
, and
Corynebacterium striatum
. Here, we have explored the survival and behavior of such microbes and find that
E. faecalis
readily survives culturing with
P. aeruginosa
while other tested species do not. In each of the tested conditions,
E. faecalis
growth remained unchanged by the presence of
P. aeruginosa
, indicating a unique mutualistic interaction between the two species. We find that
E. faecalis
proximity leads
P. aeruginosa
to attenuate competitive behaviors as exemplified by reduced production of
Pseudomonas
quinolone signal and pyocyanin. Reduced alkyl quinolones are important to
E. faecalis
as these will grow in supernatant from a quinolone mutant but not
P. aeruginosa
wild-type in planktonic culture. The reduced pyocyanin production of
P. aeruginosa
is attributable to production of ornithine by
E. faecalis
, which we recapitulate by adding exogenous ornithine to
P. aeruginosa
monocultures. Similarly, co-culture with an ornithine-deficient strain of
E. faecalis
leads
P. aeruginosa
to yield near monoculture amounts of pyocyanin. Here, we directly demonstrate how notorious pathogens such as
P. aeruginosa
might persist in polymicrobial infections under the influence of metabolites produced by other bacterial species.

IMPORTANCE

While we now appreciate that many infections are polymicrobial, we understand little of the specific actions between a given set of microbes to enable combinatorial survival and pathogenesis. The bacteria
Pseudomonas aeruginosa
and
Enterococcus faecalis
are both prevalent pathogens in wound, urinary tract, and bacteremic infections. While
P. aeruginosa
often kills other species in standard laboratory culture conditions, we present here that
E. faecalis
can be reliably co-cultured with
P. aeruginosa
. We specifically detail that ornithine produced by
E. faecalis
reduces the
Pseudomonas
quinolone signal response of
P. aeruginosa
. This reduction of the
Pseudomonas
quinolone signal response aids
E. faecalis
growth.
Inorganic polyphosphate and the stringent response coordinately control cell division and cell morphology in
Escherichia coli
Authors: Hamm Christopher W. , Gray Michael J. 
Published: December 2024

ABSTRACT

Bacteria encounter numerous stressors in their constantly changing environments and have evolved many methods to deal with stressors quickly and effectively. One well-known and broadly conserved stress response in bacteria is the stringent response, mediated by the alarmone (p)ppGpp. (p)ppGpp is produced in response to amino acid starvation and other nutrient limitations and stresses and regulates both the activity of proteins and expression of genes.
Escherichia coli
also makes inorganic polyphosphate (polyP), an ancient molecule evolutionary conserved across most bacteria and other cells, in response to a variety of stress conditions, including amino acid starvation. PolyP can act as an energy and phosphate storage pool, metal chelator, regulatory signal, and chaperone, among other functions. Here we report that
E. coli
lacking both (p)ppGpp and polyP have a complex phenotype indicating previously unknown overlapping roles for (p)ppGpp and polyP in regulating cell division, cell morphology, and metabolism. Disruption of either (p)ppGpp or polyP synthesis led to the formation of filamentous cells, but simultaneous disruption of both pathways resulted in cells with heterogenous cell morphologies, including highly branched cells, severely mislocalized Z-rings, and cells containing substantial void spaces. These mutants also failed to grow when nutrients were limited, even when amino acids were added. These results provide new insights into the relationship between polyP synthesis and the stringent response in bacteria and point toward their having a joint role in controlling metabolism, cell division, and cell growth.

IMPORTANCE

Cell division is a fundamental biological process, and the mechanisms that control it in
Escherichia coli
have been the subject of intense research scrutiny for many decades. Similarly, both the (p)ppGpp-dependent stringent response and inorganic polyphosphate (polyP) synthesis are well-studied, evolutionarily ancient, and widely conserved pathways in diverse bacteria. Our results indicate that these systems, normally studied as stress-response mechanisms, play a coordinated and novel role in regulating cell division, morphology, and metabolism even under non-stress conditions.
A bacterial membrane-disrupting protein stimulates animal metamorphosis
Authors: Malter Kyle E. , Dunbar Tiffany L. , Westin Carl , Darin Emily , Alfaro Josefa Rivera , Shikuma Nicholas J. 
Published: December 2024

ABSTRACT

Diverse marine animals undergo a metamorphic larval-to-juvenile transition in response to surface-bound bacteria. Although this host-microbe interaction is critical to establishing and maintaining marine animal populations, the functional activity of bacterial products and how they activate the host’s metamorphosis program has not yet been defined for any animal. The marine bacterium
Pseudoalteromonas luteoviolacea
stimulates the metamorphosis of a tubeworm called
Hydroides elegans
by producing a molecular syringe called metamorphosis-associated contractile structures (MACs). MACs stimulate metamorphosis by injecting a protein effector termed metamorphosis-inducing factor 1 (Mif1) into tubeworm larvae. Here, we show that MACs bind to tubeworm cilia and form visible pores on the cilia membrane surface, which are smaller and less numerous in the absence of Mif1.
In vitro
, Mif1 associates with eukaryotic lipid membranes and possesses phospholipase activity. MACs can also deliver Mif1 to human cell lines and cause parallel phenotypes, including cell surface binding, membrane disruption, calcium flux, and mitogen-activated protein kinase activation. Finally, MACs can also stimulate metamorphosis by delivering two unrelated membrane-disrupting proteins, MLKL and RegIIIɑ. Our findings demonstrate that membrane disruption by MACs and Mif1 is necessary for
Hydroides
metamorphosis, connecting the activity of a bacterial protein effector to the developmental transition of a marine animal.

IMPORTANCE
This research describes a mechanism wherein a bacterium prompts the metamorphic development of an animal from larva to juvenile form by injecting a protein that disrupts membranes in the larval cilia. Specifically, results show that a bacterial contractile injection system and the protein effector it injects form pores in larval cilia, influencing critical signaling pathways like mitogen-activated protein kinase and calcium flux, ultimately driving animal metamorphosis. This discovery sheds light on how a bacterial protein effector exerts its activity through membrane disruption, a phenomenon observed in various bacterial toxins affecting cellular functions, and elicits a developmental response. This work reveals a potential strategy used by marine organisms to respond to microbial cues, which could inform efforts in coral reef restoration and biofouling prevention. The study’s insights into metamorphosis-associated contractile structures’ delivery of protein effectors to specific anatomical locations highlight prospects for future biomedical and environmental applications.
High-quality draft genomes of ecologically and geographically diverse
Psilocybe
species
Authors: Bollinger Ian M. , Singer Harte , Jacobs Jordan , Tyler Marshall , Scott Kelsey , Pauli Christopher S. , Miller Dusty Rose , Barlow Caine , Rockefeller Alan , Slot Jason C. , Angel-Mosti Victor 
Published: December 2024

ABSTRACT

Psilocybe
is a genus of mushroom-forming fungi with ecological, ethnomycological, and clinical importance due to psilocybin production by most species. We present five genomes that enable deeper discovery and analysis of the psilocybin gene cluster and increase taxonomic resolution within
Psilocybe
:
Psilocybe semilanceata
,
Psilocybe gandalfiana
nom. prov.,
Psilocybe caeruleorhiza
,
Psilocybe azurescens
, and
Psilocybe allenii
.
Genome assembly and annotation of microalga
Nannochloropsis oceanica
C018
Authors: Estrada-Graf Adrian , Koneru Hari , Arnold Jason , Calhoun Sara , Grigoriev Igor V. , Johnson Zackary I. 
Published: December 2024

ABSTRACT

The microalga
Nannochloropsis
is an important organism for algae-based biocommodity production of food, feed, and fuel, among other products. Using PacBio Revio, we sequenced, assembled, and annotated a 26.41 Mbp
Nannochloropsis oceanica
C018 genome.
Amplicon sequences of sourdough starter cultures treated with varying levels of water chlorination
Authors: Lau Pearson , Jain Swapan , Peraza Rei , Perron Gabriel G. 
Published: December 2024

ABSTRACT

Here, we present amplicon sequences from sourdough starter cultures that have been treated with a chlorine concentration gradient mirroring public water distribution systems. Data derived present insights into the effect of important environmental factors that may influence the formation of microbial communities in food biomes.
Complete genome sequence of
Dorea formicigenerans
JCM 31256
Authors: Tourlousse Dieter M. , Murotomi Kazutoshi , Hamajima Mayu , Sekiguchi Yuji 
Published: December 2024

ABSTRACT

We describe a complete genome sequence of
Dorea formicigenerans
JCM 31256. The genome consists of a single circular chromosome with a length of 3,090,452 base pairs and a GC content of 40.8%, and was predicted to contain 3,061 total genes, encoding for 2,907 proteins.
Phenotypic and genotypic characterization of clinical carbapenem-resistant
Acinetobacter
species harboring the metallo-beta-lactamases IMP-8 or NDM-1 in China
Authors: Xu Qingye , Mu Xinli , He Jintao , Liu Haiyang , Liu Xiaochen , Wang Yanfei , Hua Xiaoting , Yu Yunsong 
Published: December 2024

ABSTRACT

Carbapenem-resistant
Acinetobacter
spp. pose a significant challenge in clinical settings due to limited treatment options for nosocomial infections. Carbapenem-hydrolyzing class D beta-lactamases are the primary cause for carbapenem resistance, while metallo-beta-lactamases (MBLs) New Delhi metallo beta-lactamase (NDM) and imipenemase (IMP) also contribute. This study investigated five MBL-producing
Acinetobacter
spp. strains isolated from a clinic in China in 2010. The
bla
IMP-8
-carrying A1014 was the first identified CRAB among all known ST
Pas
150 isolates worldwide. Through whole-genome sequencing and the southern blot analysis, we determined that
bla
IMP-8
was located on a pR4WN-type plasmid and
bla
NDM-1
was located on four distinct pSU1904NDM-type plasmids. The
bla
IMP-8
gene was identified within a class 1 integron organized as a 5’-conserved segment (
intI
), variable region (
bla
IMP-8
-
aac(6')-Ib
), and 3’-conserved segment (
qacE
Δ1/
sul1
). All available sequences of
bla
IMP
variants in
A. baumannii
from the NCBI were investigated and classified into five types of class 1 integrons. All
bla
NDM-1
plasmids were transferable, and the
bla
NDM-1
genes were in a conservative region. Additionally, multiple resistance genes, including those conferring resistance to aminoglycosides, tetracyclines, and macrolides, were detected on plasmids from these strains. All strains were resistant to meropenem and imipenem, while they were all susceptible to tigecycline and intermediate to polymyxin. A207 and A1014 were susceptible to cefiderocol, and only
bla
IMP-8
-carrying A1014 had low MIC value (4/2 µg/mL) toward cefoperazone/sulbactam. In conclusion, we characterized the phenotypic and genotypic features of one IMP-8-producing and four NDM-1-producing plasmids recovered from
Acinetobacter
spp. strains isolated in 2010, contributing to the understanding of the dissemination and evolution of these enzymes.

IMPORTANCE

Given the low prevalence of IMP among
A. baumannii
and the limited sequencing technology in earlier years, research on
bla
IMP
in
A. baumannii
is scarce, and genetic information on
bla
NDM-1
-producing
Acinetobacter
spp. strains isolated in earlier years is limited. This study revisited five MBL-carrying
Acinetobacter
spp. strains isolated in 2010, characterizing their phenotypic and genotypic features. This retrospective analysis serves as a form of “bacterial archaeology,” providing evidence of the evolutionary changes in genetic elements conferring antibiotic resistance.
Predicting complications in elderly patients undergoing oral cancer resection with free flap reconstruction in China: a retrospective cohort study using the modified Frailty Index and Prognostic Nutritional Index
Authors: Luo Tao , Huang Can , Zhou Ren , Sun Yu 
Published: December 2024

ObjectivesThis study aimed to evaluate the predictive abilities of the 5-item modified Frailty Index (5-mFI), Prognostic Nutrition Index (PNI), and their combination in older adult patients undergoing oral cancer resection and free flap reconstruction.DesignRetrospective cohort study.SettingSecondary care involving multiple centres treating older adult patients for oral cancer.ParticipantsThis study included a total of 1197 patients aged ≥60 years who underwent oral cancer resection with free flap reconstruction between January 2014 and December 2022. The study included patients aged ≥60 years with malignant tumours who underwent selective radical surgery, such as mandibulectomy, maxillectomy, glossectomy or laryngectomy, followed by free flap reconstruction under general anaesthesia. Exclusion criteria included the presence of any inflammatory disease affecting blood test results, incomplete clinical records or missing data for any of the five items in the 5-mFI. Patients were categorised into four groups based on PNI and 5-mFI values: (1) ‘Control’ (neither frail nor malnourished), (2) ‘Frailty’ (frail only), (3) ‘Malnutrition’ (malnourished only) and (4) ‘Frailty+Malnutrition’ (both frail and malnourished).Primary and secondary outcome measuresThe primary outcome was the rate of complications within 30 days after surgery. Secondary outcomes included unplanned reoperation rates, length of postoperative hospital stay and the predictive performance of PNI, 5-mFI and their combination.ResultsThe overall complication rate within 30 days post-surgery was 34.6%. The Frailty+Malnutrition group exhibited the highest risk of complications, longer postoperative hospital stays and increased rates of unplanned reoperation compared with the Control, Frailty and Malnutrition groups. The combined PNI and 5-mFI model significantly improved the predictive value for postoperative complications compared with either PNI or 5-mFI alone.ConclusionsOlder adult patients undergoing oral cancer resection with free flap reconstruction face considerable risk from frailty and malnutrition. Although both 5-mFI and PNI independently demonstrated good predictive abilities for postoperative complications, the combined model provided the best prediction. These findings could help optimise preoperative management in this high-risk population.
Exploring the status of online social support for older adults with cancer: a scoping review protocol
Authors: Liu Fei , Pilleron Sophie , Pinker India 
Published: December 2024

IntroductionThe estimated number of new cases among older adults with cancer has been increasing. Considering the decrease in social networks as adults age, their need for social support is often unmet. Notably, an increasing number of older adults with cancer have access to social support through online technologies, especially since the COVID-19 pandemic, which heightened the need for online social support. Little is known, however, about the extent to which online social support for older people with cancer has developed. This scoping review aims to explore the developments in online social support for older adults with cancer.Methods and analysisWe will search PubMed, Elsevier Embase (including Medline) and EBSCO CINAHL Complete to identify eligible studies based on predefined criteria. Screening of articles and data extraction will be carried out independently by two reviewers, with conflicts resolved by a third reviewer. This scoping review will be based on the Arksey and O’Malley methodological framework with the extension proposed by Levac and colleagues. The review findings will be presented in a narrative analysis using tables. This protocol is registered on Open Science Framework athttps://doi.org/10.17605/OSF.IO/Z9XJ7.Ethics and disseminationNo ethical approval is needed. The findings will be published in a peer-reviewed journal and presented at conferences.