bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased mutations in lipopolysaccharide biosynthetic genes cause time-dependent development of phage resistance in
Salmonella
Authors: Yu Jing , Zhang Haoyu , Ju Zijing , Huang Jiaqi , Lin Cong , Wu Jie , Wu Yingting , Sun Shuhong , Wang Hongning , Hao Guijuan , Zhang Anyun 
Published: January 2024

ABSTRACT

Understanding how bacteria evolve resistance to phages has implications for phage-based therapies and microbial evolution. In this study, the susceptibility of 335
Salmonella
isolates to the wide host range
Salmonella
phage BPSELC-1 was tested. Potentially significant gene sets that could confer resistance were identified using bioinformatics approaches based on phage susceptibility phenotypes; more than 90 potential antiphage defense gene sets, including those involved in lipopolysaccharide (LPS) biosynthesis, DNA replication, secretion systems, and respiratory chain, were found. The evolutionary dynamics of
Salmonella
resistance to phage were assessed through laboratory evolution experiments, which showed that phage-resistant mutants rapidly developed and exhibited genetic heterogeneity. Most representative
Salmonella
hosts (58.1% of 62) rapidly developed phage resistance within 24 h. All phage-resistant mutant clones exhibited genetic heterogeneity and observed mutations in LPS-related genes (
rfaJ
and
rfaK
) as well as other genes such as cellular respiration, transport, and cell replication-related genes. The study also identified potential trade-offs, indicating that bacteria tend to escape fitness trade-offs through multi-site mutations, all tested mutants increased sensitivity to polymyxin B, but this does not always affect their relative fitness or biofilm-forming capacity. Furthermore, complementing the
rfaJ
mutant gene could partially restore the phage sensitivity of phage-resistant mutants. These results provide insight into the phage resistance mechanisms of
Salmonella
and the complexity of bacterial evolution resulting from phage predation, which can inform future strategies for phage-based therapies and microbial evolution.
Natural transformation-specific DprA coordinate DNA double-strand break repair pathways in heavily irradiated
D. radiodurans
Authors: Sharma Dhirendra Kumar , Soni Ishu , Misra Hari S. , Rajpurohit Yogendra Singh 
Published: January 2024

ABSTRACT

Deinococcus radiodurans
exhibits remarkable survival under extreme conditions, including ionizing radiation, desiccation, and various DNA-damaging agents. It employs unique repair mechanisms, such as single-strand annealing (SSA) and extended synthesis-dependent strand annealing (ESDSA), to efficiently restore damaged genome. In this study, we investigate the role of the natural transformation-specific protein DprA in DNA repair pathways following acute gamma radiation exposure. Our findings demonstrate that the absence of DprA leads to rapid repair of gamma radiation-induced DNA double-strand breaks primarily occur through SSA repair pathway. Additionally, our findings suggest that the DprA protein may hinder both the SSA and ESDSA repair pathways, albeit in distinct manners. Overall, our results highlight the crucial function of DprA in the selection between SSA and ESDSA pathways for DNA repair in heavily irradiated
D. radiodurans
.

IMPORTANCE

Deinococcus radiodurans
exhibits an extraordinary ability to endure and thrive in extreme environments, including exposure to radiation, desiccation, and damaging chemicals, as well as intense UV radiation. The bacterium has evolved highly efficient repair mechanisms capable of rapidly mending hundreds of DNA fragments in its genome. Our research indicates that natural transformation (NT)-specific
dprA
genes play a pivotal role in regulating DNA repair in response to radiation. Remarkably, we found that DprA is instrumental in selecting DNA double-strand break repair pathways, a novel function that has not been reported before. This unique regulatory mechanism highlights the indispensable role of DprA beyond its native function in NT and underscores its ubiquitous presence across various bacterial species, regardless of their NT proficiency. These findings shed new light on the resilience and adaptability of
Deinococcus radiodurans
, opening avenues for further exploration into its exceptional survival strategies.
The critical roles of propanethiol oxidoreductase and sulfide-quinone oxidoreductase in the propanethiol catabolism pathway in
Pseudomonas putida
S-1
Authors: Qiao Pei , Ning Lixiao , Chen Jinhui , Tang Yuhang , Zhao Rui , Chen Guoqing , Ye Qun , Zhou Tong , Chen Jianmeng , Zhong Weihong 
Published: January 2024

ABSTRACT

Propanethiol (PT) is a hazardous pollutant that poses risks to both the environment and human well-being.
Pseudomonas putida
S-1 has been identified as a microorganism capable of utilizing PT as its sole carbon source. However, the metabolic pathway responsible for PT degradation in
P. putida
S-1 has remained poorly understood, impeding its optimization and practical application. In this study, we investigated the catabolic network involved in PT desulfurization with
P. putida
S-1 and identified key gene modules crucial to this process. Notably, propanethiol oxidoreductase (PTO) catalyzes the initial degradation of PT, a pivotal step for
P. putida
S-1’s survival on PT. PTO facilitates the oxidation of PT, resulting H
2
S, H
2
O
2
, and propionaldehyde (PA). Catalase-peroxidase catalyzes the conversion of H
2
O
2
to oxygen and water, while PA undergoes gradual conversion to Succinyl-CoA, which is subsequently utilized in the tricarboxylic acid cycle. H
2
S is digested in a comprehensive desulfurization network where sulfide-quinone oxidoreductase (SQOR) predominantly converts it to sulfane sulfur. The transcriptome analysis suggests that sulfur can be finally converted to sulfite or sulfate and exported out of the cell. The PT degradation capacity of
P. putida
S-1 was enhanced by increasing the transcription level of PTO and SQOR genes
in vivo
.

IMPORTANCE

This work investigated the PT catabolism pathway in
Pseudomonas putida
S-1, a microorganism capable of utilizing PT as the sole carbon source. Critical genes that control the initiation of PT degradation were identified and characterized, such as
pto
and
sqor
. By increasing the transcription level of
pto
and
sqor
genes
in vivo
, we have successfully enhanced the PT degradation efficiency and growth rate of
P. putida
S-1. This work does not only reveal a unique PT degradation pathway but also highlights the potential of enhancing the microbial desulfurization process in the bioremediation of thiol-contaminated environment.
Control of asparagine homeostasis in
Bacillus subtilis
: identification of promiscuous amino acid importers and exporters
Authors: Meißner Janek , Königshof Manuel , Wrede Katrin , Warneke Robert , Mardoukhi Mohammad Saba Yousef , Commichau Fabian M. , Stülke Jörg 
Published: January 2024

ABSTRACT

The Gram-positive model bacterium
B. subtilis
is able to import all proteinogenic amino acids from the environment as well as to synthesize them. However, the players involved in the acquisition of asparagine have not yet been identified for this bacterium. In this work, we used
d
-asparagine as a toxic analog of
l
-asparagine to identify asparagine transporters. This revealed that
d
- but not
l
-asparagine is taken up by the malate/lactate antiporter MleN. Specific strains that are sensitive to the presence of
l
-asparagine due to the lack of the second messenger cyclic di-AMP or due to the intracellular accumulation of this amino acid were used to isolate and characterize suppressor mutants that were resistant to the presence of otherwise growth-inhibiting concentrations of
l
-asparagine. These screens identified the broad-spectrum amino acid importers AimA and BcaP as responsible for the acquisition of
l
-asparagine. The amino acid exporter AzlCD allows detoxification of
l
-asparagine in addition to 4-azaleucine and histidine. This work supports the idea that amino acids are often transported by promiscuous importers and exporters. However, our work also shows that even stereo-enantiomeric amino acids do not necessarily use the same transport systems.

IMPORTANCE

Transport of amino acid is a poorly studied function in many bacteria, including the model organism
Bacillus subtilis
. The identification of transporters is hampered by the redundancy of transport systems for most amino acids as well as by the poor specificity of the transporters. Here, we apply several strategies to use the growth-inhibitive effect of many amino acids under defined conditions to isolate suppressor mutants that exhibit either reduced uptake or enhanced export of asparagine, resulting in the identification of uptake and export systems for
l
-asparagine. The approaches used here may be useful for the identification of transporters for other amino acids both in
B. subtilis
and in other bacteria.
Biological characterization and genomic analysis of a novel methicillin-resistant
Staphylococcus aureus
phage, SauPS-28
Authors: Zhao Peisong , Zhao Wenli , Zhai Xin , He Yulin , Shu Wei , Qiao Guanhua 
Published: January 2024

ABSTRACT

Staphylococcus aureus,
a representative gram-positive bacterium, is a common infectious pathogen widely present in the natural environment. The increasing application of antibiotics is witnessing an increment in the number of clinically resistant strains (such as methicillin-resistant
S. aureus
[MRSA]), which has posed a great challenge to antimicrobial therapy. In this study, a novel MRSA phage, SauPS-28, was isolated from the lake water of the Guangxi Zhuang Autonomous Region. This phage has an incubation period of approximately 30 min, a lysis period of approximately 40 min, and a burst size of approximately 25 PFU/cell. The isolated phage exhibited good biological stability at a pH range of 6.0–9.0 and temperature range of 4°C–37°C. In addition, the identification of an elongated tail using transmission electron microscopy confirmed that SauPS-28 belongs to the long-tailed phage family. Whole-genome sequencing analysis revealed that SauPS-28 has a 43,286-bp-long genome with 31.03% G + C content. Moreover, SauPS-28 exhibited 95.69% sequence identity with ECel-2020k, while the query coverage was only 66%, which is a newly discovered phage. Whole-genome functional annotation results revealed that SauPS-28 had 68 open reading frames (ORFs). Of these, 30 ORFs are unknown proteins. The results suggest that SauPS-28 could be a lysogenic phage strain. This study thus provides preliminary data to conduct further in-depth analysis of the mechanism of phage–host interaction and provides a reference value for phage therapy.

IMPORTANCE

In recent years, drug-resistant bacterial infections have become increasingly serious. As a kind of virus with the ability to infect and lyse drug-resistant bacteria, phage is expected to be a new therapeutic method. In this study, we isolated and purified a new methicillin-resistant
Staphylococcus aureus
bacteriophage SauPS-28, studied a series of biological characteristics of the bacteriophage, analyzed the genome and structural proteome data of the bacteriophage, and provided reference data for further study of the interaction mechanism between bacteriophage and host bacteria and promoted new antibacterial strategies.
Effect of nasal carriage of
Bacillus
species on COVID-19 severity: a cross-sectional study
Authors: Fowora Muinah A. , Aiyedogbon Adenike , Omolopo Ibilola , Tajudeen Ahmed O. , Olanlege Abdul-Lateef , Abioye Adefunke , Akintunde Grace B. , Salako Babatunde L. 
Published: January 2024

ABSTRACT

Intranasal sprays containing
Bacillus
species are being researched for treating viral respiratory tract infections. The aim of this study was to assess the relationship between the nasal carriage of
Bacillus
and COVID-19 severity. This was a cross-sectional study that collected nasopharyngeal samples from adults 18 years and above visiting two COVID-19 testing centers in Lagos, Nigeria, between September 2020 and September 2021.
Bacillus
species were cultured from the samples and confirmed using 16 s rRNA gene sequencing. The dependent variable was COVID-19 status classified as negative, asymptomatic, mild, or severe. The independent variable was the nasal carriage of
Bacillus
species. Multinomial regression analysis was done to determine the association between nasal carriage of
Bacillus
and COVID-19 severity after adjusting for age, sex, and co-morbidity status. A total of 388 participants were included in the study with mean (standard deviation) age of 40.05 (13.563) years. Sixty-one percent of the participants were male, 100 (25.8%) had severe COVID-19, 130 (33.5%) had pre-existing comorbidity, and 76 (19.6%) had
Bacillus
cultured from their nasopharyngeal specimen.
Bacillus
species presence was significantly associated with higher odds of severe COVID-19 compared to having a negative COVID-19 status (AOR = 3.347, 95% CI: 1.359, 8.243). However, the presence of
Bacillus
species was significantly associated with lower odds of severe COVID-19 compared to having a mild COVID-19 status. The study suggests that nasal carriage of
Bacillus
species is associated with the clinical course of COVID-19 and supports the exploration of
Bacillus
species in the management of viral respiratory tract infections.

IMPORTANCE

With the introduction of intranasal spray containing
Bacillus
species for the treatment of viral respiratory tract infections, such as COVID-19 and respiratory syncytial virus, identifying the association between the nasal carriage of
Bacillus
species and COVID-19 susceptibility and severity will help further substantiate the investigation of these bacteria for COVID-19 prevention and treatment. This study evaluated the association between the carriage of
Bacillus
species in the nasopharyngeal tract and COVID-19 severity and found that the presence of
Bacillus
species in the nasopharynx may significantly impact the clinical course of COVID-19.
Exercise prescription variables predict reductions in pain intensity in adults with chronic low back pain: secondary analysis of a randomised controlled trial
Authors: Neason Christopher , Miller Clint T , Tagliaferri Scott D , Belavy Daniel L , Main Luana C , Ford Jon J , Hahne Andrew J , Bowe Steven J , Owen Patrick J 
Published: January 2024

ObjectivesThe relationship between exercise training variables and clinical outcomes in low back pain (LBP) is unclear. The current study aimed to explore the relationship between exercise training parameters and pain intensity in individuals with chronic LBP.MethodsThis study is a secondary analysis of a previously reported randomised controlled trial comparing the effects of general strength and conditioning to motor control exercises and manual therapy. This secondary analysis includes adults with chronic LBP (n=20) randomised to the general strength and conditioning programme only. Primary outcomes of this analysis were exercise training parameters (time under tension, rating of perceived exertion (RPE), session duration, session-RPE and training frequency) and pain intensity (0–100 mm visual analogue acale) measured every 2 weeks from baseline to 6 months follow-up. Linear mixed models with random effects (participants) and allowance for heterogeneity of variance (study date) were used to determine the association between pain intensity and training parameters over time.ResultsMean (95% CI) pain intensity decreased over time from baseline to 6 months follow-up by 10.7 (2.8 to 18.7) points (p=0.008). Over the 6-month intervention, lower pain intensity was associated with higher RPE (β (95% CI) −27.168 (−44.265 to –10.071), p=0.002), greater time under tension (−0.029 (–0.056 to –0.001), p=0.040) and shorter session duration (1.938 (0.011 to 3.865), p=0.049).ConclusionDuring 6 months of general strength and conditioning, lower pain intensity was associated with higher participant-reported training intensity, greater volume and shorter session duration. To ensure positive outcomes to exercise training, these variables should be monitored on a short-term basis.Trial registration numberACTRN12615001270505.
The deterministic pattern matching based on the parameterized quantum circuit
Authors: Liu Lu , Wu Xing-Yu , Xu Chu-Yao , Zhang Lu-Fan , Wang Chuan 
Published: January 2024

AbstractGrover quantum algorithm is an unstructured search algorithm that can run on a quantum computer with the complexity of O$\sqrt{N}$

N

, and is one of the typical algorithms of quantum computing. Recently, it has served as a routine for pattern-matching tasks. However, the original Grover search algorithm is probabilistic, which is not negligible for problems involving determinism. Besides that, efficient data loading is also a key challenge for the practical applications of the Grover algorithm. Here in this work, we propose a modified pattern-matching scheme with Long’s quantum search algorithm, in which the quantum circuit structure search algorithm requires fewer multi-qubit quantum gates, and can obtain the desired results deterministically. Then, the comparison of the performance of our scheme and the previous algorithms is presented through numerical simulations, indicating our algorithm is feasible with current quantum technologies which is friendly to noisy intermediate-scale quantum (NISQ) devices.
PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis
Authors: Xu Xiaonan , Bok Ilah , Jasani Neel , Wang Kaizhen , Chadourne Manon , Mecozzi Nicol , Deng Ou , Welsh Eric A. , Kinose Fumi , Rix Uwe , Karreth Florian A. 
Published: January 2024

Abstract

Inactivating mutations in PTEN are prevalent in melanoma and are thought to support tumor development by hyperactivating the AKT/mTOR pathway. Conversely, activating mutations in AKT are relatively rare in melanoma, and therapies targeting AKT or mTOR have shown disappointing outcomes in preclinical models and clinical trials of melanoma. This has led to the speculation that PTEN suppresses melanoma by opposing AKT-independent pathways, potentially through noncanonical functions beyond its lipid phosphatase activity. In this study, we examined the mechanisms of PTEN-mediated suppression of melanoma formation through the restoration of various PTEN functions in PTEN-deficient cells or mouse models. PTEN lipid phosphatase activity predominantly inhibited melanoma cell proliferation, invasion, and tumor growth, with minimal contribution from its protein phosphatase and scaffold functions. A drug screen underscored the exquisite dependence of PTEN-deficient melanoma cells on the AKT/mTOR pathway. Furthermore, activation of AKT alone was sufficient to counteract several aspects of PTEN-mediated melanoma suppression, particularly invasion and the growth of allograft tumors. Phosphoproteomics analysis of the lipid phosphatase activity of PTEN validated its potent inhibition of AKT and many of its known targets, while also identifying the AP-1 transcription factor FRA1 as a downstream effector. The restoration of PTEN dampened FRA1 translation by inhibiting AKT/mTOR signaling, and FRA1 overexpression negated aspects of PTEN-mediated melanoma suppression akin to AKT. This study supports AKT as the key mediator of PTEN inactivation in melanoma and identifies an AKT/mTOR/FRA1 axis as a driver of melanomagenesis.

Significance:
PTEN suppresses melanoma predominantly through its lipid phosphatase function, which when lost, elevates FRA1 levels through AKT/mTOR signaling to promote several aspects of melanomagenesis.
Abstract B007: Mutations in chromatin remodelers produce intra-chromosomal deletions in cancer cells
Authors: Hamid Abdulaziz B. , Frank Lauren E. , Nelakurti Devi D. , Valentine Anna , Kaur Mehak , Latif Ali , Bouley Renee A. , Petreaca Ruben C. 
Published: January 2024

Abstract
Cancer cells are characterized by chromosomal re-arrangements which range from small deletions and insertions (InDels) to complete genome re-organization such as kataegis and chromothripsis. These genomic re-arrangements accompanied by other mutation signatures act as drivers of cellular transformation and immortalization. One form of re-arrangement is the intra-chromosomal deletion (ICD) which is larger than an InDel and can wipe out entire genomic sequences. Recurrent ICDs have been shown to inactivate key cell cycle regulators (e.g., Rb, PTEN, TP53) and contribute to cellular transformation. However, cancer cells are replete with ICDs of unknown function. ICDs arise due to failure of the DNA double strand break (DSB) repair machinery but the mechanism remains elusive. Mutations in three Mutations in key DNA damage repair genes such as the breast cancer susceptibility genes BRCA1 and BRCA2 as well as the accessory gene RAD52 accelerate ICD formation. Using the yeast model system, we identified physical and genetic interactions between RAD52 and two chromatin remodeling factors (KAT5 and HIRA). KAT5 is a histone acetyltransferase with functions in both transcription and DSB repair while HIRA is a histone chaperone required for re-deposition of nucleosomes following repair. We will present results from computational analysis of cancer genomes as well as experimental bench data that show that mutations in KAT5 and HIRA affect ICD formation. Epistatic analysis between the histone remodelers and BRCA1, BRCA2 and RAD52 reveals that co-occurring mutations contribute to destabilization of the repair machinery. In silico protein structure analysis was performed to model how mutations affect the function of these enzymes. Our data uncovers unexpected functions of chromatin remodelers in modulating the function of DNA recombinases and other accessory factors.
Citation Format: Abdulaziz B. Hamid, Lauren E. Frank, Devi D. Nelakurti, Anna Valentine, Mehak Kaur, Ali Latif, Renee A. Bouley, Ruben C. Petreaca. Mutations in chromatin remodelers produce intra-chromosomal deletions in cancer cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B007.