bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salmonella
Typhimurium infection inhibits macrophage IFNβ signaling in a TLR4-dependent manner
Authors: Shuster Michael , Lyu Zhihui , Augenstreich Jacques , Mathur Shrestha , Ganesh Akshaya , Ling Jiqiang , Briken Volker 
Published: September 2024

ABSTRACT

Type I Interferons (IFNs) generally have a protective role during viral infections, but their function during bacterial infections is dependent on the bacterial species.
Legionella pneumophila
,
Shigella sonnei
and
Mycobacterium tuberculosis
can inhibit type I IFN signaling. Here we examined the role of type I IFN, specifically IFNβ, in the context of
Salmonella enterica
serovar Typhimurium (STm) macrophage infections and the capacity of STm to inhibit type I IFN signaling. We demonstrate that IFNβ has no effect on the intracellular growth of STm in infected bone marrow derived macrophages (BMDMs) derived from C57BL/6 mice. STm infection inhibits IFNβ signaling but not IFNγ signaling in a murine macrophage cell line. We show that this inhibition is independent of the type III and type VI secretion systems expressed by STm and is also independent of bacterial phagocytosis. The inhibition is Toll-like receptor 4 (TLR4)-dependent as the TLR4 ligand, lipopolysaccharide (LPS), alone is sufficient to inhibit IFNβ-mediated signaling. Cells downregulated their surface levels of IFNα/β receptor 1 (IFNAR1) in response to LPS, which may be mediating our observed inhibition. Lastly, we examined this inhibition in the context of TLR4-deficient BMDMs as well as TLR4 RNA interference and we observed a loss of inhibition with LPS stimulation as well as STm infection. In summary, we show that macrophages exposed to STm have reduced IFNβ signaling via crosstalk with TLR4 signaling, which may be mediated by reduced host cell surface IFNAR1, and that IFNβ signaling does not affect cell-autonomous host defense against STm.
Graduate teaching assistants’ beliefs and practices regarding mentoring in the context of an online introductory biology CURE: an exploratory study
Authors: Santillan Karen A. , Rediske Andrea M. , Olimpo Jeffrey T. 
Published: September 2024

ABSTRACT

Course-based undergraduate research experiences (CUREs) have been identified as a promising approach to engage large numbers of students in discovery-based investigations in the biological sciences. As the prevalence of CUREs continues to increase nationwide, the role of graduate teaching assistants (TAs) in facilitating these courses has simultaneously grown. In addition to serving as instructors of CUREs, previous research suggests that educators—including TAs—must also adopt additional roles, including that of a mentor. However, few studies have explicitly examined CURE TAs’ beliefs and practices regarding mentorship. To address this need, we conducted an exploratory, concurrent mixed methods study to better understand TAs’ self-reported mentoring skills levels and their experiences acting as potential mentors in the context of an online introductory biology SEA-PHAGES CURE. Results indicate that TAs (
N
= 12) believed themselves most skilled in areas related to listening and communication, building rapport with students, and encouraging independence with respect to student research projects. Analysis of open-ended survey data further demonstrated that the overwhelming majority of TAs (
n
= 10) considered themselves to be mentors, citing a diversity of rationales reflective of both psychosocial and instrumental forms of mentoring support. Collectively, these outcomes contribute to a growing body of literature on the nature and level of involvement of TAs within CURE learning environments, particularly with respect to their posited role as mentors.
Fibroblast stromal support model for predicting human papillomavirus-associated cancer drug responses
Authors: James Claire D. , Lewis Rachel L. , Fakunmoju Alexis L. , Witt Austin J. , Youssef Aya H. , Wang Xu , Rais Nabiha M. , Prabhakar Apurva T. , Machado J. Mathew , Otoa Raymonde , Bristol Molly L. 
Published: September 2024

ABSTRACT

Currently, there are no specific antiviral therapeutic approaches targeting Human papillomaviruses (HPVs), which cause around 5% of all human cancers. Specific antiviral reagents are particularly needed for HPV-related oropharyngeal cancers (HPV
+
OPCs) whose incidence is increasing and for which there are no early diagnostic tools available. We and others have demonstrated that the estrogen receptor alpha (ERα) is overexpressed in HPV
+
OPCs, compared to HPV-negative cancers in this region, and that these elevated levels are associated with an improved disease outcome. Utilizing this HPV
+
-specific overexpression profile, we previously demonstrated that estrogen attenuates the growth and cell viability of HPV
+
keratinocytes and HPV
+
cancer cells
in vitro
. Expansion of this work
in vivo
failed to replicate this sensitization. The role of stromal support from the tumor microenvironment (TME) has previously been tied to both the HPV lifecycle and
in vivo
therapeutic responses. Our investigations revealed that
in vitro
co-culture with fibroblasts attenuated HPV
+
-specific estrogen growth responses. Continuing to monopolize on the HPV
+
-specific overexpression of ERα, our co-culture models then assessed the suitability of the selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen, and showed growth attenuation in a variety of our models to one or both of these drugs
in vitro
. Utilization of these SERMs
in vivo
closely resembled the sensitization predicted by our co-culture models. Therefore, the
in vitro
fibroblast co-culture model better predicts
in vivo
responses. We propose that utilization of our co-culture
in vitro
model can accelerate cancer therapeutic drug discovery.

IMPORTANCE

Human papillomavirus-related cancers (HPV
+
cancers) remain a significant public health concern, and specific clinical approaches are desperately needed. In translating drug response data from
in vitro
to
in vivo
, the fibroblasts of the adjacent stromal support network play a key role. Our study presents the utilization of a fibroblast 2D co-culture system to better predict translational drug assessments for HPV
+
cancers. We also suggest that this co-culture system should be considered for other translational approaches. Predicting even a portion of treatment paradigms that may fail
in vivo
with a co-culture model will yield significant time, effort, resource, and cost efficiencies.
Feeling hormonal? Insights into bacterial auxin sensing and its physiological effects
Authors: van der Meij Anne 
Published: September 2024

ABSTRACT

Plant–microbe communication involves a rich language of chemical signals. Among these signals are plant hormones such as auxins, which are primarily recognized for their roles in plant development. However, they also function in modulating plant–microbe interactions. Interestingly, many bacteria are capable of producing auxins too. Yet, the mechanisms by which auxins affect bacteria and the regulatory processes controlling their production are largely unknown. Rico-Jiménez and colleagues present new insights into the effects of the auxin indole-3-acetic acid on the physiology of the rhizobacterium
Serratia plymuthica
(M. Rico-Jiménez, Z. Udaondo, T. Krell, and M. A. Matilla, mSystems 9:e00165-24, 2024,
https://doi.org/10.1128/msystems.00165-24
). Their work provides a deeper mechanistic understanding of bacterial transcriptional responses to plant hormones and the impact on bacterial fitness in the context of the rhizosphere environment.
In vitro
evaluation of the automated hematology analyzer XN-31 for rapid diagnosis of equine piroplasmosis
Authors: Ochi Akihiro , Toya Yuji , Sengoku Mikako , Tsuchiya Seiichiro , Kishi Daiki , Ueno Takanori 
Published: September 2024

ABSTRACT

Equine piroplasmosis (EP) is a protozoal disease affecting equids, caused by
Theileria equi
and
Babesia caballi
. EP is conventionally diagnosed using microscopic, molecular, and/or serological methods, which are time-consuming. Consequently, there is a need for faster testing methods. In this study, we evaluated the application of the Sysmex XN-31 automated hematology analyzer, originally a rapid test for detecting malaria in humans, for the diagnosis of EP. The cultured parasites were measured using the XN-31 that had been customized for horse blood samples (XN-31m). The following parameters were evaluated: limit of detection (LoD), limit of quantification (LoQ), linearity, carryover, precision, and correlation with microscopic examination. The XN-31m detected infected red blood cells (RBCs) in approximately 1 minute. The LoD and LoQ for
B. caballi
were 4.54 infected RBCs/μL and 14.10 infected RBCs/μL, while those for
T. equi
were 5.80 infected RBCs/μL and 11.44 infected RBCs/μL, respectively. Linearity showed excellent correlation (
R
2
> 0.99), and carryover never exceeded 0.5%. The coefficient of variation was under 5%. The correlation between the results obtained using XN-31m and microscopic examination was high (
R
2
> 0.98). In conclusion, the XN-31 analyzer detected
B. caballi
and
T. equi
parasites in approximately 1 minute with high sensitivity. The results indicate the potential of the XN-31 analyzer as a fast and user-friendly diagnostic method for EP.

IMPORTANCE

In this study, we demonstrated that the automated hematology analyzer, XN-31, can detect red blood cells infected with
Babesia caballi
and
Theileria equi
in about 1 minute. We evaluated the diagnostic performance of the XN-31 analyzer for equine piroplasmosis, providing evidence of its potential as a diagnostic tool for this disease.
Selection for amoxicillin-, doxycycline-, and enrofloxacin-resistant
Escherichia coli
at concentrations lower than the ECOFF in broiler-derived cecal fermentations
Authors: Swinkels Aram F. , Fischer Egil A. J. , Korving Lisa , Kusters Nina E. , Wagenaar Jaap A. , Zomer Aldert L. 
Published: September 2024

ABSTRACT

Antimicrobial resistance (AMR) is an emerging worldwide problem and a health threat for humans and animals. Antimicrobial usage in human and animal medicine or in agriculture results in selection for AMR. The selective concentration of antimicrobial compounds can be lower than the minimum inhibitory concentration and differs between environments, which can be a reason for bacterial resistance. Therefore, knowledge of the minimal selective concentration (MSC), under natural conditions, is essential to understand the selective window of bacteria when exposed to residual antimicrobials. In this study, we estimated the MSCs of three antimicrobials, amoxicillin, doxycycline, and enrofloxacin in a complex microbial community by conducting fermentation assays with cecal material derived from broilers. We examined the phenotypic resistance of
Escherichia coli
, resistome, and microbiome after 6 and 30 hours of fermenting in the presence of the antimicrobials of interest. The concentrations were estimated to be 10–100 times lower than the epidemiological cut-off values in
E. coli
for the respective antimicrobials as determined by EUCAST, resulting in an MSC between 0.08 and 0.8 mg/L for amoxicillin, 0.4 and 4 mg/L for doxycycline, and 0.0125 and 0.125 mg/L for enrofloxacin. Additionally, resistome analysis provided an MSC for doxycycline between 0.4 and 4 mg/L, but amoxicillin and enrofloxacin exposure did not induce a significant difference. Our findings indicate at which concentrations there is still selection for antimicrobial-resistant bacteria. This knowledge can be used to manage the risk of the emergence of antimicrobial-resistant bacteria.

IMPORTANCE
Antimicrobial resistance possibly affects human and animal health, as well as economic prosperity in the future. The rise of antimicrobial-resistant bacteria is a consequence of using antimicrobial compounds in humans and animals selecting for antimicrobial-resistant bacteria. Concentrations reached during treatment are known to be selective for resistant bacteria. However, at which concentrations residues are still selective is important, especially for antimicrobial compounds that remain in the environment at low concentrations. The data in this paper might inform decisions regarding guidelines and regulations for the use of specific antimicrobials. In this study, we are providing these minimal selective concentrations for amoxicillin, doxycycline, and enrofloxacin in complex environments.
Microbial interactions impact stress tolerance in a model oral community
Authors: Lewin Gina R. , Evans Emma R. , Whiteley Marvin 
Published: September 2024

ABSTRACT

Understanding the molecular mechanisms governing microbial interactions is crucial for unraveling the complexities of microbial communities and their ecological impacts. Here, we employed a two-species model system comprising the oral bacteria
Aggregatibacter actinomycetemcomitans
and
Streptococcus gordonii
to investigate how synergistic and antagonistic interactions between microbes impact their resilience to environmental change and invasion by other microbes. We used an
in vitro
colony biofilm model and focused on two
S
.
gordonii
-produced extracellular molecules, L-lactate and H
2
O
2
, which are known to impact fitness of this dual-species community. While the ability of
A. actinomycetemcomitans
to cross-feed on
S. gordonii
-produced L-lactate enhanced its fitness during co-culture, this function showed little impact on the ability of co-cultures to resist environmental change. In fact, the ability of
A. actinomycetemcomitans
to catabolize L-lactate may be detrimental in the presence of tetracycline, highlighting the complexity of interactions under antimicrobial stress. Furthermore, H
2
O
2
, known for its antimicrobial properties, had negative impacts on both species in our model system. However, H
2
O
2
production by
S. gordonii
enhanced
A. actinomycetemcomitans
tolerance to tetracycline, suggesting a protective role under antibiotic pressure. Finally,
S. gordonii
significantly inhibited the bacterium
Serratia marcescens
from invading
in vitro
biofilms, but this inhibition was lost during co-culture with
A. actinomycetemcomitans
and in a murine abscess model, where
S. gordonii
actually promoted
S. marcescens
invasion. These data indicate that microbial interactions can impact fitness of a bacterial community upon exposure to stresses, but these impacts are highly environment dependent.

IMPORTANCE

Microbial interactions are critical modulators of the emergence of microbial communities and their functions. However, how these interactions impact the fitness of microbes in established communities upon exposure to environmental stresses is poorly understood. Here, we utilized a two-species community consisting of
Aggregatibacter actinomycetemcomitans
and
Streptococcus gordonii
to examine the impact of synergistic and antagonistic interactions on microbial resilience to environmental fluctuations and susceptibility to microbial invasion. We focused on the
S. gordonii
-produced extracellular molecules, L-lactate and H
2
O
2
, which have been shown to mediate interactions between these two microbes. We discovered that seemingly beneficial functions, such as
A. actinomycetemcomitans
cross-feeding on
S. gordonii
-produced L-Lactate, can paradoxically exacerbate vulnerabilities, such as susceptibility to antibiotics. Moreover, our data highlight the context-dependent nature of microbial interactions, emphasizing that a seemingly potent antimicrobial, such as H
2
O
2
, can have both synergistic and antagonistic effects on a microbial community dependent on the environment.
Molecular characterization of a novel putative pathogen,
Streptococcus nakanoensis
sp. nov., isolated from sputum culture
Authors: Wajima Takeaki , Sugawara Takashi , Tanaka Emi , Uchiya Kei-ichi 
Published: September 2024

ABSTRACT

Reports of novel species of α-hemolytic
Streptococcus
have increased recently. However, limited information exists regarding the pathogenicity of these species, with the exception of
Streptococcus pneumoniae
and
Streptococcus pseudopneumoniae
. In this study, a quinolone-resistant α-
Streptococcus
strain, MTG105, was isolated from the sputum of a patient with pneumonia. This strain was first identified as
S. pneumoniae
at the hospital laboratory; however, it exhibited unique genetic features upon further analysis. Digital DNA-DNA hybridization and average nucleotide identity based on BLAST values from whole-genome sequencing revealed MTG105 to be a novel species closely related to
S. pseudopneumoniae
. Although MTG105 carried two copies of the pneumolysin gene, similar to
S. pseudopneumoniae
, this isolate exhibited susceptibility to optochin under both aerobic and 5% CO
2
conditions. Notably, no biochemical features could be used to definitively identify this species. In an infection assay using organotypic lung tissue models, MTG105 induced epithelial damage comparable to that of
S. pneumoniae
and
S. pseudopneumoniae
, possibly suggesting its potential as a pathogenic α-
Streptococcus
. The natural transformation abilities of
Streptococcus
species facilitate their exchange of genes within the same genus, resulting in the existence of species with increasingly more diverse genome structures. Therefore, the identification of this species highlights the importance of monitoring the emergence of novel species exhibiting virulence and/or multidrug resistance. This isolate was proposed as a novel species, designated
Streptococcus nakanoensis
sp. nov. The type strain was MTG 105
T
(= JCM 35953
T
= CCUG 76894
T
).

IMPORTANCE

The genus
Streptococcus
encompasses a wide range of bacteria with more than 60 species. Recently, there has been a notable increase in reports of novel species of α-
Streptococcus
based on genomic analysis data. However, limited information exists regarding the pathogenicity of these species. In this study, a quinolone-resistant α-hemolytic
Streptococcus
strain, MTG105, was isolated from a patient with pneumonia. Genetic analysis revealed that this species was a novel species closely related to
S. pseudopneumoniae
. In an infection assay using organotypic lung tissue models, MTG105 induced epithelial damage comparable to that caused by
S. pneumoniae
and
S. pseudopneumoniae
, strongly suggesting its potential as a pathogenic α-
Streptococcus
. The natural transformation abilities of
Streptococcus
species facilitate gene exchange within the same genus, leading to the emergence of species with increasingly diverse genome structures. Therefore, the identification of this species underscores the importance of monitoring the emergence of novel species exhibiting virulence and/or multidrug resistance.
Protein and transcriptional biomarker profiling may inform treatment strategies in lower respiratory tract infections by indicating bacterial–viral differentiation
Authors: Sivakumaran Dhanasekaran , Jenum Synne , Markussen Dagfinn Lunde , Serigstad Sondre , Srivastava Aashish , Saghaug Christina Skår , Ulvestad Elling , Knoop Siri Tandberg , Grewal Harleen M. S. 
Published: September 2024

ABSTRACT

Lower respiratory tract infections (LRTIs) remain a significant global cause of infectious disease-related mortality. Accurate discrimination between acute bacterial and viral LRTIs is crucial for optimal patient care, prevention of unnecessary antibiotic prescriptions, and resource allocation. Plasma samples from LRTI patients with bacterial (
n
= 36), viral (
n
= 27; excluding SARS-CoV-2), SARS-CoV-2 (
n
= 22), and mixed bacterial–viral (
n
= 38) etiology were analyzed for protein profiling. Whole-blood RNA samples from a subset of patients (bacterial,
n
= 8; viral,
n
= 8; and SARS-CoV-2,
n
= 8) were analyzed for transcriptional profiling. Lasso regression modeling identified a seven-protein signature (CRP, IL4, IL9, IP10, MIP1α, MIP1β, and TNFα) that discriminated between patients with bacterial (
n
= 36) vs viral (
n
= 27) infections with an area under the curve (AUC) of 0.98. When comparing patients with bacterial and mixed bacterial–viral infections (antibiotics clinically justified;
n
= 74) vs patients with viral and SARS-CoV-2 infections (antibiotics clinically not justified;
n
= 49), a 10-protein signature (CRP, bFGF, eotaxin, IFNγ, IL1β, IL7, IP10, MIP1α, MIP1β, and TNFα) with an AUC of 0.94 was identified. The transcriptional profiling analysis identified 232 differentially expressed genes distinguishing bacterial (
n
= 8) from viral and SARS-CoV-2 (
n
= 16) etiology. Protein–protein interaction enrichment analysis identified 20 genes that could be useful in the differentiation between bacterial and viral infections. Finally, we examined the performance of selected published gene signatures for bacterial–viral differentiation in our gene set, yielding promising results. Further validation of both protein and gene signatures in diverse clinical settings is warranted to establish their potential to guide the treatment of acute LRTIs.

IMPORTANCE
Accurate differentiation between bacterial and viral lower respiratory tract infections (LRTIs) is vital for effective patient care and resource allocation. This study investigated specific protein signatures and gene expression patterns in plasma and blood samples from LRTI patients that distinguished bacterial and viral infections. The identified signatures can inform the design of point-of-care tests that can aid healthcare providers in making informed decisions about antibiotic prescriptions in order to reduce unnecessary use, thereby contributing to reduced side effects and antibiotic resistance. Furthermore, the potential for faster and more accurate diagnoses for improved patient management in acute LRTIs is compelling.
Estimating size-at-harvest from Indigenous archaeological clamshell assemblages in Coastal British Columbia
Authors: Hillis Dylan , Barclay Kristina M. , Foster Erin , Kobluk Hannah M. , Vollman Taylor , Salomon Anne K. , Darimont Chris T. , McKechnie Iain 
Published: September 2024

Shellfish have supported Indigenous lifeways on the Pacific Coast of North America for millennia. Despite the ubiquity of clamshells in archaeological sites, shell size measurements are rarely reported due to a lack of applicable basis for generating size estimates from fragmentary remains. We present a linear regression-based method for determining shell length from hinge and umbo measurements of littleneck ( Leukoma staminea; n = 239), butter ( Saxidomus gigantea; n = 274), and horse ( Tresus nuttallii; n = 92) clams using both contemporary and archaeological shells collected from three regions in coastal British Columbia, Canada. We examine the accuracy of these size estimations, which indicate that 83%–97% of the variability in dorsal shell length is predicted by umbo thickness and hinge length. Hinge length generated higher R2 values yet exhibited greater intra- and inter-observer error. While the predicted dorsal length for each species differed by region, this size difference was smaller than intra- and inter-observer error, suggesting broad applicability for these simple measurements. We applied these formulae to a Tseshaht First Nation archaeological clamshell assemblage ( n = 488) on western Vancouver Island spanning 3000 years and observed profiles that resemble contemporary legal size limits, which suggests the sustained use and maintenance of local shellfisheries. The accuracy of these regression models for determining shell length from fragments highlights the utility of this approach as a basis for assessing past shellfish management practices.