bluuebunny/crossref_metadata_2025_split huggingface dataset:
Escherichia coli
CadB is capable of promiscuously transporting muropeptides and contributing to peptidoglycan recycling
Authors: Simpson Brent W. , Gilmore Michael C. , McLean Amanda Briann , Cava Felipe , Trent M. Stephen 
Published: January 2024

ABSTRACT

The bacterial peptidoglycan (PG) cell wall is remodeled during growth and division, releasing fragments called muropeptides. Muropeptides can be internalized and reused in a process called PG recycling.
Escherichia coli
is highly devoted to recycling muropeptides and is known to have at least two transporters, AmpG and OppBCDF, that import them into the cytoplasm. While studying mutants lacking AmpG, we unintentionally isolated mutations that led to the altered expression of a third transporter, CadB. CadB is normally upregulated under acidic pH conditions and is an antiporter for lysine and cadaverine. Here, we explored if CadB was altering PG recycling to assist in the absence of AmpG. Surprisingly, CadB overexpression was able to restore PG recycling when both AmpG and OppBCDF were absent. CadB was found to import freed PG peptides, a subpopulation of muropeptides, through a promiscuous activity. Altogether, our data support that CadB is a third transporter capable of contributing to PG recycling.

IMPORTANCE

Bacteria produce a rigid mesh cell wall. During growth, the cell wall is remodeled, which releases cell wall fragments. If released into the extracellular environment, cell wall fragments can trigger inflammation by the immune system of a host. Gastrointestinal bacteria, like
Escherichia coli
, have dedicated pathways to recycle almost all cell wall fragments they produce.
E. coli
contains two known recycling transporters, AmpG and Opp, that we previously showed are optimized for growth in different environments. Here, we identify that a third transporter, CadB, can also contribute to cell wall recycling. This work expands our understanding of cell wall recycling and highlights the dedication of organisms like
E. coli
to ensure high recycling in multiple growth environments.
SNX32 is a host restriction factor that degrades African swine fever virus CP204L via the RAB1B-dependent autophagy pathway
Authors: Yang Wenping , Li Lingxia , Zhang Jing , Wu Junhuang , Kang Weifang , Wang Yue , Ding Haiyan , Li Dan , Zheng Haixue 
Published: January 2024

ABSTRACT
African swine fever virus (ASFV) causes a highly contagious and deadly disease in domestic pigs and European wild boars, posing a severe threat to the global pig industry. ASFV CP204L, a highly immunogenic protein, is produced during the early stages of ASFV infection. However, the impact of CP204L protein-interacting partners on the outcome of ASFV infection is poorly understood. To accomplish this, coimmunoprecipitation and mass spectrometry analysis were conducted in ASFV-infected porcine alveolar macrophages (PAMs). We have demonstrated that sorting nexin 32 (SNX32) is a CP204L-binding protein and that CP204L interacted and colocalized with SNX32 in ASFV-infected PAMs. ASFV growth and replication were promoted by silencing SNX32 and suppressed by overexpressing SNX32. SNX32 degraded CP204L by recruiting the autophagy-related protein Ras-related protein Rab-1b (RAB1B). RAB1B overexpression inhibited ASFV replication, while knockdown of RAB1B had the opposite effect. Additionally, RAB1B, SNX32, and CP204L formed a complex upon ASFV infection. Taken together, this study demonstrates that SNX32 antagonizes ASFV growth and replication by recruiting the autophagy-related protein RAB1B. This finding extends our understanding of the interaction between ASFV CP204L and its host and provides new insights into exploring the relationship between ASFV infection and autophagy.

IMPORTANCE

African swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease with a high mortality near 100% in domestic pigs. ASF virus (ASFV), which is the only member of the family
Asfarviridae
, is a dsDNA virus of great complexity and size, encoding more than 150 proteins. Currently, there are no available vaccines against ASFV. ASFV CP204L represents the most abundantly expressed viral protein early in infection and plays an important role in regulating ASFV replication. However, the mechanism by which the interaction between ASFV CP204L and host proteins affects ASFV replication remains unclear. In this study, we demonstrated that the cellular protein SNX32 interacted with CP204L and degraded CP204L by upregulating the autophagy-related protein RAB1B. In summary, this study will help us understand the interaction mechanism between CP204L and its host upon infection and provide new insights for the development of vaccines and antiviral drugs.
Dietary supplementation with
Lactiplantibacillus plantarum
P-8 improves the growth performance and gut microbiota of weaned piglets
Authors: Yu Jie , Zuo Bin , Li Qi , Zhao Feiyan , Wang Junjun , Huang Weiqiang , Sun Zhihong , Chen Yongfu 
Published: January 2024

ABSTRACT

Weaning is a stressful event in the pig life cycle. We hypothesized that probiotics could be potential alternatives to antibiotics for promoting growth and ameliorating stress in weaning piglets via gut microbiota modulation and, thus, investigated the beneficial effects of dietary probiotic supplementation in weaning pigs. Ninety weaning piglets (Landrace × large white, 45 males and 45 females, 25 days of age) were randomized into three dietary treatments (30 piglets/treatment, divided into five replicates/treatment, i.e., six piglets/replicate) in this 28-day trial: control (C group, basal diet); probiotic [lactic acid bacteria (LAB) group, basal diet plus
Lactiplantibacillus plantarum
P-8]; and antibiotic (A group; basal diet plus chlortetracycline). The piglets’ growth performance [average daily gain, average daily feed intake (ADFI), and feed conversion ratio (FCR)], immune and antioxidant markers, ileal mucosal morphology, and ileal and colonic microbiomes were compared among treatment groups. Compared to the C and A groups, probiotic supplementation significantly decreased the ADFI, FCR, and ileal mucosal crypt depth while increasing the villus height-to-crypt depth ratio, hepatic glutathione peroxidase and catalase activities, and serum levels of interleukin-2. Both probiotic and antibiotic treatments modulated the piglets’ gut microbiomes, with more
L. plantarum
in the LAB group and more
Eubacterium rectale
and
Limosilactobacillus reuteri
in the A group. Probiotic supplementation significantly increased the relative abundance of genes encoding the acetylene, galactose, and stachyose degradation pathways, potentially enhancing nutrient absorption, energy acquisition, and growth performance. Probiotics are effective alternatives to antibiotics for promoting the health of piglets, possibly via gut microbiome modulation.

IMPORTANCE

Weaning impacts piglet health, performance, and mortality. Antibiotic treatment during weaning can mitigate the negative effects on growth. However, antibiotic use in livestock production contributes to the emergence of antibiotic resistance, which is a threat to global public health. This comprehensive study describes the gut microbial composition and growth performance of weaned piglets after dietary supplementation with
Lactiplantibacillus plantarum
P-8 or antibiotics.
L. plantarum
P-8 ameliorated stress and improved antioxidant capacity and growth performance in weaned piglets, accompanied by gut microbiota improvement.
L. plantarum
P-8 is an effective substitute for antibiotics to promote the health of weaned piglets while avoiding the global concern of drug resistance.
SMR peptide antagonizes
Staphylococcus aureus
biofilm formation
Authors: Huang Ming-Bo , Brena Dara , Wu Jennifer Y. , Shelton Martin , Bond Vincent C. 
Published: January 2024

ABSTRACT

The emergence and international dissemination of multi-drug resistant
Staphylococcus aureus
(
S. aureus
) strains challenge current antibiotic-based therapies, representing an urgent threat to public health worldwide. In the U.S. alone,
S
.
aureus
infections are responsible for 11,000 deaths and 500,000 hospitalizations annually. Biofilm formation is a major contributor to antibiotic tolerance and resistance-induced delays in empirical therapy with increased infection severity, frequency, treatment failure, and mortality. Developing novel treatment strategies to prevent and disrupt biofilm formation is imperative. In this article, we test the Secretion Modification Region (SMR) peptides for inhibitory effects on resistant
S. aureus
biofilm-forming capacity by targeting the molecular chaperone DnaK. The dose effect of SMR peptides on biofilm formation was assessed using microtiter plate methods and confocal microscopy. Interaction between the antagonist and DnaK was determined by immune precipitation with anti-Flag M2 Affinity and Western blot analysis. Increasing SMR peptide concentrations exhibited increasing blockade of
S. aureus
biofilm formation with significant inhibition found at 18 µM, 36 µM, and 72 µM. This work supports the potential therapeutic benefit of SMR peptides in reducing biofilm viability and could improve the susceptibility to antimicrobial agents.

IMPORTANCE
The development of anti-biofilm agents is critical to restoring bacterial sensitivity, directly combating the evolution of resistance, and overall reducing the clinical burden related to pervasive biofilm-mediated infections. Thus, in this study, the SMR peptide, a novel small molecule derived from the HIV Nef protein, was preliminarily explored for anti-biofilm properties. The SMR peptide was shown to effectively target the molecular chaperone DnaK and inhibit biofilm formation in a dose-dependent manner. These results support further investigation into the mechanism of SMR peptide-mediated biofilm formation and inhibition to benefit rational drug design and the identification of therapeutic targets.
Comparative reassessment of AcrB efflux inhibitors reveals differential impact of specific pump mutations on the activity of potent compounds
Authors: Schuster Sabine , Vavra Martina , Wirth Dave A. N. , Kern Winfried V. 
Published: January 2024

ABSTRACT

Multidrug resistance poses global challenges, particularly with regard to Gram-negative bacterial infections. In view of the lack of new antibiotics, drug enhancers, such as efflux pump inhibitors (EPIs), have increasingly come into focus. A number of chemically diverse agents have been reported to inhibit AcrB, the main multidrug transporter in
Escherichia coli
, and homologs in other Gram-negative bacteria. However, due to the often varying methodologies used for their characterization, results remain difficult to compare. In this study, using a defined selection of antibiotics known to be efflux substrates, we reevaluated 38 published compounds for their
in vitro
EPI activity. When examined in an
E. coli
strain with stable wild-type AcrB overexpression, we found 17 compounds showing at least fourfold enhancing potency with more than 2 out of 10 test drugs (belonging to eight antibiotic classes). Pyranopyridines (MBX series) were confirmed as the most potent inhibitors among agents reported so far. A new and surprising finding was that their activity, unlike that of the pyridylpiperazine EPI BDM88855, was highly susceptible to the AcrB double-mutation G141D_N282Y, which had previously been shown to diminish drug enhancing of 1-(1-naphthylmethyl)piperazine in a predominantly substrate-specific manner. Conversely, transmembrane region mutation V411A, while eliminating the drug potentiating of the BDM compound, did not decrease the activity of the MBX EPIs. Besides comparative reassessment of the potency of reported EPIs, the study demonstrated the usefulness of mutagenesis approaches providing tools for an initial discrimination of EPIs regarding their mode of function.

IMPORTANCE

Infections with difficult-to-treat multidrug-resistant bacteria pose an urgent global threat in view of the stagnating development of new antimicrobial substances. Efflux pumps in Gram-negative pathogens are known to substantially contribute to multidrug resistance making them promising targets for chemotherapeutic interventions to restore the efficacy of conventional antibiotics. In the present study, the
in vitro
activity of previously reported efflux pump inhibitors was reassessed using standardized conditions. Relevant drug sensitizing activity could be proven for almost half of the tested compounds. Further characterization of potent inhibitors was achieved by investigating the impact of specific efflux pump mutations. A double-mutation previously known to decrease the activity of the arylpiperazine 1-(1-naphthylmethyl)piperazine also impaired that of the highly efficient pyranopyridine efflux pump inhibitors. Our findings provide direct comparability of reported efflux pump inhibitors and contribute to the elucidation of their mode of action.
Prophage enhances the ability of deep-sea bacterium
Shewanella psychrophila
WP2 to utilize D-amino acid
Authors: Tan Xiaoli , Zhang Mujie , Liu Shunzhang , Xiao Xiang , Zhang Yu , Jian Huahua 
Published: January 2024

ABSTRACT

Prophages are prevalent in the marine bacterial genomes and reshape the physiology and metabolism of their hosts. However, whether and how prophages influence the microbial degradation of D-amino acids (D-AAs), which is one of the widely distributed recalcitrant dissolved organic matters (RDOMs) in the ocean, remain to be explored. In this study, we addressed this issue in a representative marine bacterium,
Shewanella psychrophila
WP2 (WP2), and its integrated prophage SP1. Notably, compared to the WP2 wild-type strain, the SP1 deletion mutant of WP2 (WP2ΔSP1) exhibited a significantly lower D-glutamate (D-Glu) consumption rate and longer lag phase when D-Glu was used as the sole nitrogen source. The subsequent transcriptome analysis identified 1,523 differentially expressed genes involved in diverse cellular processes, especially that multiple genes related to inorganic nitrogen metabolism were highly upregulated. In addition, the dynamic profiles of ammonium, nitrate, and nitrite were distinct between the culture media of WP2 and WP2ΔSP1. Finally, we provide evidence that SP1 conferred a competitive advantage to WP2 when D-Glu was used as the sole nitrogen source and SP1-like phages may be widely distributed in the global ocean. Taken together, these findings offer novel insight into the influences of prophages on host metabolism and RDOM cycling in marine environments.

IMPORTANCE

This work represents the first exploration of the impact of prophages on the D-amino acid (D-AA) metabolism of deep-sea bacteria. By using
S. psychrophila
WP2 and its integrated prophage SP1 as a representative system, we found that SP1 can significantly increase the catabolism rate of WP2 to D-glutamate and produce higher concentrations of ammonium, resulting in faster growth and competitive advantages. Our findings not only deepen our understanding of the interaction between deep-sea prophages and hosts but also provide new insights into the ecological role of prophages in refractory dissolved organic matter and the nitrogen cycle in deep oceans.
Luteolin attenuates
Staphylococcus aureus
-induced endometritis through inhibiting ferroptosis and inflammation via activating the Nrf2/GPX4 signaling pathway
Authors: Gao Shouyang , Gao Yongjian , Cai Lifu , Qin Rui 
Published: January 2024

ABSTRACT

Endometritis, a local inflammatory disease, has been known as the most common cause of infertility in mares. In this study, we investigated the protective effects of luteolin on endometritis induced by
Staphylococcus aureus
(
S. aureus
) and further clarified the possible molecular mechanisms. An
S. aureus
–induced endometritis model was established by the infusion of
S. aureus
into the uterus. Luteolin was intraperitoneally administered to mice 1 h before
S. aureus
treatment. The results showed that the mice of the
S. aureus
group showed severe histological changes of uterine tissues, increased myeloperoxidase (MPO) activity, and elevated TNF-α, IL-1β, and IL-6 levels. These changes induced by
S. aureus
were dose-dependently inhibited by luteolin. Furthermore, luteolin inhibited MDA and Fe
2+
production and increased the production of GSH decreased by
S. aureus
. Luteolin prevented
S. aureus
–induced endometrial barrier disruption through up-regulating ZO-1 and occludin expression. Luteolin dramatically inhibited
S. aureus
–induced NF-κB activation. The expression of Nrf2 and HO-1 was increased by luteolin. In addition, the inhibitory effects of luteolin on
S. aureus
–induced endometritis were reversed in Nrf2 knockdown mice. In conclusion, these data indicated that luteolin protected mice against
S. aureus
–induced endometritis through inhibiting inflammation and ferroptosis via regulating the Nrf2 signaling pathway.

IMPORTANCE

Endometritis is an inflammatory disease of the endometrium, which is a common gynecological disease. Up to now, there is no evidence for the protective effects of luteolin on endometritis. The purpose of this study was to investigate whether luteolin has protective effects against
S. aureus
–induced endometritis and attempts to clarify the mechanism.
Levetiracetam: A Potent Sword against Microglia Polarization in Gliomas
Authors: Cui Xiaoteng , Wang Qixue , Liu Xiaomin , Kang Chunsheng 
Published: January 2024

SummaryCrosstalk between tumor cells and peritumoral cells contributes to immunosuppressive microenvironment formation in glioblastomas (GBM). A recent study revealed that glioma stem cells activated neuronal activity to promote microglial M2 polarization, leading to GBM progression, which could be pharmacologically blocked by levetiracetam, providing a practical strategy for GBM immunotherapy.See related article by Guo et al., p. 1160
Cultivating The Research Culture Mediated by Motivation Factors in Enhancing Teachers’ Performance in Conducting Action Research
Authors: Esturas Maricel D. 
Published: January 2024

Nowadays, the Department of Education recently displayed an anticipated and overwhelming interest in developing a research culture. DepEd promoted action research and encouraged teachers to engage, thus this is timely to address the learning gaps during pandemic. With this set up, teachers ought to be involved in it to foster evidence-based practice and raise research productivity. The major objective of this study was to ascertain how the research culture and motivating elements of action research to improve teachers' research performance in the selected elementary school.
The study was conducted at sixty-two schools in the division of San Pablo City using the ex post facto research design. A total of 750 elementary teachers randomly selected comprised the respondents of the study.
The correlation between motivational factors and research skills and research productivity of teachers were all significantly related. The highest correlation in terms of data analysis can be seen evidently in personal satisfaction. This reveals that teachers engaged in research activities when chances are given to utilize their skills and the administration supports the presentation of research papers. The performance and research productivity of the teachers' research abilities and efforts have a significant indirect impact on the motivational variables involved in the research. The end result of this study signifies that the relationship between the research organizational culture and teacher research performance could be enhanced by improving the motivational factors and research skills.
Exploring The Factors Influencing Learners’ Attitudes and Engagement Towards Learning Outcomes in Araling PanlipunanAmong Grade 10 Learners
Authors: Gonzales Bernadette T. , Hermosa Jherwin P. 
Published: January 2024

his study aimed to discern the factors influencing attitudes and engagement towards learning Araling Panlipunan in terms of instructional methods, classroom environment, the difficulty of the subject, teachers' behavior, learning resources, teaching competency, learning style, and integration of technology. Moreover, it also determined the level of the learning outcomes in Araling Panlipunan as cognitive, behavioral, and attitudinal. The study utilized a descriptive research design to collect quantifiable information that can be used to make statistical inferences about the target audience through data analysis. Stratified Random Sampling was used to identify 127 grade 10 learners from San Isidro Integrated National Highschool in the Schools Division of Lipa City. The data were gathered using a survey questionnaire which was validated with the help of the experts.
Findings revealed that there is a significant relationship between instructional methods and the learning outcomes in Araling Panlipunan as to Cognitive, Behavioral, and Attitudinal. The classroom environment was found to have highly significant relationships with cognitive, behavioral, and attitudinal learning outcomes in Araling Panlipunan. The difficulty of the subject has a highly significant relationship with cognitive and attitudinal learning outcomes. As for teacher behavior, highly significant relationships were recognized about cognitive, behavioral, and attitudinal Learning Outcomes in Araling Panlipunan. However, after all the data was gathered and calculated, the result revealed that there is no significant relationship between the Difficulty of the Subject and Behavioral Learning Outcomes in Araling Panlipunan.
Teacher-Mediated Pronunciation Instruction: Its Effects on Enhancing the Oral Language Fluency of Seventh-Grade English Students
Authors: Barrun Jason S. , Sia Jonald B. 
Published: January 2024

This study investigated the effects of teacher-mediated pronunciation instruction on enhancing the oral language fluency of seventh-grade English students. Using a quasi-experimental pretest-posttest non-equivalent groups design, 32 learners served as respondents of the thirteen-session- study in a secondary school in Southern Luzon, Philippines. The student-respondents were tested to find out whether there would be a significant difference in their knowledge and application of the segmentals and suprasegmentals before and after the implementation of the said intervention.
In all the instruments, namely the dictation test, pronunciation achievement test, and aural-oral achievement test, the findings revealed that the experimental group performed significantly higher than the control group. Through the independent sample t-test and Analysis of Covariance (ANCOVA), the results revealed that the experimental group had higher mean scores than the control group with t-computed values exceeding the tabular values affirming that an explicit pronunciation instruction is better in enhancing the oral language fluency of students than only incidental acquisition. The more the learners are exposed to an intervention, the more that they will become intelligible. Other effects also include the more frequently that the teacher conducts various games, the more that the students enjoy and learn pronunciation; and the more refined a learner’s pronunciation skill is, the more improved he/she is when it comes to listening comprehension and spelling. Finally, it is recommended that more and newer interventions regarding second language phonology or any content that focuses on speaking as a macro-strand in English should be delved into.