bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity at single nucleotide to pangenome scales among sulfur cycling bacteria in salt marshes
Authors: Pérez Castro Sherlynette , Peredo Elena L. , Mason Olivia U. , Vineis Joseph , Bowen Jennifer L. , Mortazavi Behzad , Ganesh Anakha , Ruff S. Emil , Paul Blair G. , Giblin Anne E. , Cardon Zoe G. 
Published: October 2023

ABSTRACT

Sulfur-cycling microbial communities in salt marsh rhizosphere sediments mediate a recycling and detoxification system central to plant productivity. Despite the importance of sulfur-cycling microbes, their biogeographic, phylogenetic, and functional diversity remain poorly understood. Here, we use metagenomic data sets from Massachusetts (MA) and Alabama (AL) salt marshes to examine the distribution and genomic diversity of sulfur-cycling plant-associated microbes. Samples were collected from sediments under
Sporobolus alterniflorus
and
Sporobolus pumilus
in separate MA vegetation zones, and under
S. alterniflorus
and
Juncus roemerianus
co-occuring in AL. We grouped metagenomic data by plant species and site and identified 38 MAGs that included pathways for sulfate reduction or sulfur oxidation. Phylogenetic analyses indicated that 29 of the 38 were affiliated with uncultivated lineages. We showed differentiation in the distribution of MAGs between AL and MA, between
S. alterniflorus
and
S. pumilus
vegetation zones in MA, but no differentiation between
S. alterniflorus
and
J. roemerianus
in AL. Pangenomic analyses of eight ubiquitous MAGs also detected site- and vegetation-specific genomic features, including varied sulfur-cycling operons, carbon fixation pathways, fixed single-nucleotide variants, and active diversity-generating retroelements. This genetic diversity, detected at multiple scales, suggests evolutionary relationships affected by distance and local environment, and demonstrates differential microbial capacities for sulfur and carbon cycling in salt marsh sediments.

IMPORTANCE
Salt marshes are known for their significant carbon storage capacity, and sulfur cycling is closely linked with the ecosystem-scale carbon cycling in these ecosystems. Sulfate reducers are key for the decomposition of organic matter, and sulfur oxidizers remove toxic sulfide, supporting the productivity of marsh plants. To date, the complexity of coastal environments, heterogeneity of the rhizosphere, high microbial diversity, and uncultured majority hindered our understanding of the genomic diversity of sulfur-cycling microbes in salt marshes. Here, we use comparative genomics to overcome these challenges and provide an in-depth characterization of sulfur-cycling microbial diversity in salt marshes. We characterize communities across distinct sites and plant species and uncover extensive genomic diversity at the taxon level and specific genomic features present in MAGs affiliated with uncultivated sulfur-cycling lineages. Our work provides insights into the partnerships in salt marshes and a roadmap for multiscale analyses of diversity in complex biological systems.
Biofilm formation and cell plasticity drive diazotrophy in an anoxygenic phototrophic bacterium
Authors: Fernández-Juárez Víctor , Hallstrøm Søren , Pacherres Cesar O. , Wang Jiaqi , Coll-Garcia Guillem , Kühl Michael , Riemann Lasse 
Published: October 2023

ABSTRACT

Non-cyanobacterial diazotrophs (NCDs) are widespread and active in marine waters. The carbon and low-oxygen (O
2
) conditions required for their N
2
fixation may be encountered on marine particles, while a putative role of light remains uninvestigated. This study explored factors that regulate N
2
fixation in
Rhodopseudomonas
sp. BAL398—a anoxygenic phototrophic bacterium isolated from low-salinity surface waters. Light (250 µmol photons m
−2
s
−1
) and anoxia (0 µM O
2
) stimulated growth and N
2
fixation; however, diazotrophy in light was dependent on high organic carbon levels (35 mM, glucose:succinate). Immunolabeling revealed that cellular nitrogenase levels increased with light, decreasing inorganic nitrogen (N) and ambient O
2
(250 µM). Light and O
2
stimulated motility and biofilm formation on surfaces, and N
2
fixation rates increased compared to the control treatment. N
2
fixation rates were positively correlated with the formation of rosette-like cellular structures, and an increased concentration of nitrogenase was observed toward the center of these structures, which increased their occurrence 600 times when cultures reached maximum N
2
fixation rates vs when they had low rates. Interestingly, N
2
fixation was not completely inhibited under oxic conditions and was accompanied by increased formation of capsules and cysts. Rosettes, as well as capsules and cysts, may thus serve as protection against O
2
. Our study reveals the physiological adaptations that underlie N
2
fixation in an anoxygenic phototroph, emphasizing the significance of biofilm formation for utilizing light and fixing N
2
under oxic conditions, and underscores the need for deciphering the importance of light for marine NCDs.

IMPORTANCE

The contribution of non-cyanobacterial diazotrophs (NCDs) to total N
2
fixation in the marine water column is unknown, but their importance is likely constrained by the limited availability of dissolved organic matter and low O
2
conditions. Light could support N
2
fixation and growth by NCDs, yet no examples from bacterioplankton exist. In this study, we show that the phototrophic NCD,
Rhodopseudomonas
sp. BAL398, which is a member of the diazotrophic community in the surface waters of the Baltic Sea, can utilize light. Our study highlights the significance of biofilm formation for utilizing light and fixing N
2
under oxic conditions and the role of cell plasticity in regulating these processes. Our findings have implications for the general understanding of the ecology and importance of NCDs in marine waters.
Bladder-draining lymph nodes support germinal center B cell responses during urinary tract infection in mice
Authors: Hawas Sophia , Vagenas Dimitrios , Haque Ashraful , Totsika Makrina 
Published: October 2023

ABSTRACT

Bacterial urinary tract infections (UTIs) are both common and exhibit high recurrence rates in women. UTI healthcare costs are increasing due to the rise of multidrug-resistant (MDR) bacteria, necessitating alternative approaches for infection control. Here, we directly observed host adaptive immune responses in acute UTI. We employed a mouse model in which wild-type C57BL/6J mice were transurethrally inoculated with a clinically relevant MDR UTI strain of uropathogenic
Escherichia coli
(UPEC). Firstly, we noted that

rag1
−/−

C57BL/6J mice harbored larger bacterial burdens than wild-type counterparts, consistent with a role for adaptive immunity in UTI control. Consistent with this, UTI triggered in the bladders of wild-type mice early increases of myeloid cells, including CD11c
hi
conventional dendritic cells, suggesting possible involvement of these professional antigen-presenting cells. Importantly, germinal center B cell responses developed by 4 weeks post-infection in bladder-draining lymph nodes of wild-type mice and, although modest in magnitude and transient in nature, could not be boosted with a second UTI. Thus, our data reveal for the first time in a mouse model that UPEC UTI induces local B cell immune responses in bladder-draining lymph nodes, which could potentially serve to control infection.
The
P. falciparum
alternative histones Pf H2A.Z and Pf H2B.Z are dynamically acetylated and antagonized by PfSir2 histone deacetylases at heterochromatin boundaries
Authors: Azizan Suffian , Selvarajah Shamista A. , Tang Jingyi , Jeninga Myriam D. , Schulz Danae , Pareek Kapil , Herr Tamara , Day Karen P. , De Koning-Ward Tania F. , Petter Michaela , Duffy Michael F. 
Published: October 2023

ABSTRACT

The
Plasmodium falciparum
alternative histones Pf H2A.Z and Pf H2B.Z are enriched in the same nucleosomes in intergenic euchromatin but depleted from heterochromatin. They occupy most promoters but are only dynamically associated with expression at
var
genes. In other organisms, acetylation of H2A.Z is important for its functions in gene expression and chromatin structure. Here, we show that acetylated Pf H2A.Z and Pf H2B.Z are dynamically associated with gene expression at promoters. In addition, acetylated Pf H2A.Z and Pf H2B.Z are antagonized by the sirtuin class III histone deacetylases (HDAC) PfSir2A and B at heterochromatin boundaries and encroach upon heterochromatin in parasites lacking PfSir2A or B. However, the majority of acetylated Pf H2A.Z and Pf H2B.Z are deacetylated by class I or II HDACs. Acetylated Pf H2A.Z and Pf H2B.Z are also dynamically associated with promoter activity of both canonical upstream
var
gene promoters and
var
gene introns. These findings suggest that both acetylated Pf H2A.Z and Pf H2B.Z play critical roles in gene expression and contribute to maintenance of chromatin structure at the boundaries of subtelomeric, facultative heterochromatin, critical for the variegated expression of genes that enable rapid adaptation to altered host environments.

IMPORTANCE

The malaria parasite
Plasmodium falciparum
relies on variant expression of members of multi-gene families as a strategy for environmental adaptation to promote parasite survival and pathogenesis. These genes are located in transcriptionally silenced DNA regions. A limited number of these genes escape gene silencing, and switching between them confers variant fitness on parasite progeny. Here, we show that PfSir2 histone deacetylases antagonize DNA-interacting acetylated alternative histones at the boundaries between active and silent DNA. This finding implicates acetylated alternative histones in the mechanism regulating
P. falciparum
variant gene silencing and thus malaria pathogenesis. This work also revealed that acetylation of alternative histones at promoters is dynamically associated with promoter activity across the genome, implicating acetylation of alternative histones in gene regulation genome wide. Understanding mechanisms of gene regulation in
P. falciparum
may aid in the development of new therapeutic strategies for malaria, which killed 619,000 people in 2021.
The transcription factor DksA exerts opposing effects on cell division depending on the presence of ppGpp
Authors: Anderson Sarah E. , Vadia Stephen E. , McKelvy Jane , Levin Petra Anne 
Published: October 2023

ABSTRACT

Bacterial cell size is a multifactorial trait that is influenced by variables including nutritional availability and the timing of cell division. Prior work revealed a negative correlation between concentration of the alarmone (p)ppGpp (ppGpp) and cell length in
Escherichia coli
, suggesting that ppGpp may promote assembly of the division machinery (divisome) and cytokinesis in this organism. To clarify this counterintuitive connection between a starvation-induced stress response effector and cell proliferation, we undertook a systematic analysis of growth and division in
E. coli
cells defective in ppGpp synthesis and/or engineered to overproduce the alarmone. Our data indicate that ppGpp acts indirectly on divisome assembly through its role as a global mediator of transcription. Loss of either ppGpp (ppGpp
0
) or the ppGpp-associated transcription factor DksA led to increased average length, with ppGpp
0
mutants also exhibiting a high frequency of extremely long filamentous cells. Using heat-sensitive division mutants and fluorescently labeled division proteins, we confirmed that ppGpp and DksA are cell division activators. We found that ppGpp and DksA regulate division through their effects on transcription, although the lack of known division genes or regulators in available transcriptomics data strongly suggests that this regulation is indirect. We also found that DksA inhibits division in ppGpp
0
cells, contrary to its role in a wild-type background. We propose that the ability of ppGpp to switch DksA from a division inhibitor to a division activator helps tune cell length across different concentrations of ppGpp.

IMPORTANCE
Cell division is a key step in the bacterial lifecycle that must be appropriately regulated to ensure survival. This work identifies the alarmone (p)ppGpp (ppGpp) as a general regulator of cell division, extending our understanding of the role of ppGpp beyond a signal for starvation and other stress. Even in nutrient-replete conditions, basal levels of ppGpp are essential for division to occur appropriately and for cell size to be maintained. This study establishes ppGpp as a “switch” that controls whether the transcription factor DksA behaves as a division activator or inhibitor. This unexpected finding enhances our understanding of the complex regulatory mechanisms employed by bacteria to coordinate division with diverse aspects of cell growth and stress response. Because division is an essential process, a better understanding of the mechanisms governing the assembly and activation of the division machinery could contribute to the development of novel therapeutics to treat bacterial infections.
Phage single-stranded DNA-binding protein or host DNA damage triggers the activation of the AbpAB phage defense system
Authors: Sasaki Takaomi , Takita Saya , Fujishiro Takashi , Shintani Yunosuke , Nojiri Satoki , Yasui Ryota , Yonesaki Tetsuro , Otsuka Yuichi 
Published: October 2023

ABSTRACT

Bacteria have developed various defense mechanisms against phages. Abortive infection (Abi), a bacterial defense mechanism, can be achieved through various means, including toxin-antitoxin systems, cyclic oligonucleotide-based antiphage signaling systems, and retrons. AbpA and AbpB (AbpAB) defend against many lytic phages harboring double-stranded DNA genomes in
Escherichia coli
; however, how AbpAB senses phage infection and inhibits its propagation remains unclear. Here, we demonstrated that AbpAB inhibited the growth of the φX174 lytic phage with single-stranded DNA (ssDNA) as well as the lysogenization and induction of the Sakai prophage 5 lysogenic phage. The AbpAB defense system limits T4 and φX174 phage propagation via Abi. AbpA contains a nuclease domain at its N-terminus, and AbpB has an ATP-dependent RNA helicase domain; both domains are required for phage defense. This system is activated by phage Gp32 binding to ssDNA and inhibits
E. coli
growth. Without phage infection, DNA replication inhibitors or defects in the DNA repair factors RecB and RecC activate this system. Therefore, the
E. coli
AbpAB defense system may sense DNA-protein complexes, including the phage-encoded ssDNA-binding protein or those formed by interrupting host DNA replication or repair.

IMPORTANCE

Although numerous phage defense systems have recently been discovered in bacteria, how these systems defend against phage propagation or sense phage infections remains unclear. The
Escherichia coli
AbpAB defense system targets several lytic and lysogenic phages harboring DNA genomes. A phage-encoded single-stranded DNA-binding protein, Gp32, activates this system similar to other phage defense systems such as Retron-Eco8, Hachiman, ShosTA, Nhi, and Hna. DNA replication inhibitors or defects in DNA repair factors activate the AbpAB system, even without phage infection. This is one of the few examples of activating phage defense systems without phage infection or proteins. The AbpAB defense system may be activated by sensing specific DNA-protein complexes.
Landscape of gut microbiota and metabolites and their interaction in comorbid heart failure and depressive symptoms: a random forest analysis study
Authors: Huang Kai , Duan Jiahao , Wang Ruting , Ying Hangfeng , Feng Qinwen , Zhu Bin , Yang Chun , Yang Ling 
Published: October 2023

ABSTRACT

Depression is an individual risk factor for poor prognosis in patients with heart failure (HF). Recent studies show that gut microbiota and metabolites play a critical role in comorbid HF and depressive symptoms. We recruited 95 subjects including 35 HF patients with depressive symptoms (HF-DS), 36 HF patients without depressive symptoms (HF-NDS), and 24 healthy controls (HC). The 16S rRNA, metagenome sequencing, and untargeted metabolomic analysis were employed to test fecal samples. Our analysis found a significant difference in composition of gut microbiota in HF-DS, HF-NDS, and HC populations. At the genus level,
Mediterranea
,
Tolumona
, and
Parabacteroides
were significantly increased in HF-DS patients compared with HF-NDS patients, while
Pedobacter
,
Azospirillum
, and
Ruminiclostridium
were significantly decreased. Furthermore, anti-inflammatory mediators (abietic acid, quinic acid, linoleic acid, etc.) and neurotransmitters (catechin, serotonin, tryptamine, phenylethylamine, etc.) were reduced in HF-DS. The enrichment analysis revealed that the gut microbiota highly conformed to the functional pathways of metabolites, and amino acid-related metabolism, fatty acid-related metabolism, and cAMP signaling pathways may be crucial biological mechanisms involved in the development of comorbid depression and HF. Finally,
Cloacibacillus
and alpha-tocopherol were determined as diagnostic markers for HF-DS patients.

IMPORTANCE

There is increasing evidence that alterations in gut microbial composition and function are associated with cardiovascular or psychiatric disease. Therefore, it is meaningful to investigate the taxonomic and functional characterization of the microbiota in HF patients who also have depressive symptoms. In this cross-sectional study,
Cloacibacillus
and alpha-tocopherol were determined as new diagnostic markers. Furthermore, intestinal microecosystem disorders are closely linked to depressive symptoms in HF patients, providing a new reference viewpoint for understanding the gut-heart/brain axis.
Oral lactoferrin administration does not impact the diversity or composition of the infant gut microbiota in a Peruvian cohort
Authors: González Luis , Paredes Sosa Jose Luis , Mosquito Susan , Filio Yesenia , Romero Pedro E. , Ochoa Theresa J. , Tsukayama Pablo 
Published: October 2023

ABSTRACT
Lactoferrin is a protein from breast milk involved in early-life microbiome assembly. It is believed to promote the growth of lactic acid-producing bacteria and inhibit pathogens by limiting iron availability and enabling an acidic environment in the gut. Previous reports suggest that oral administration of lactoferrin in neonates promotes the increase of gut microbiota diversity and the enrichment of beneficial microbes. However, its effect on infant gut microbiota over time has yet to be thoroughly studied to fully understand its potential as a prebiotic. Using 16s rRNA gene amplicon sequencing, we analyzed the gut microbiota composition of 60 toddlers at 12–18 months of age from Lima, Peru, who received daily oral administration of lactoferrin or placebo for 6 months since enrollment. Samples were analyzed at 0, 2, and 4 months after beginning treatment. Our results show that lactoferrin treatment does not increase gut microbiota diversity over time nor affect its bacterial composition compared to the placebo group.

IMPORTANCE
Previous studies have suggested that oral lactoferrin enhances diversity in the gut microbiota in infants while inhibiting the growth of opportunistic pathogens. However, the effect of lactoferrin on infant gut microbiota over time has yet to be thoroughly studied. Our study suggests that lactoferrin oral treatment in infants aged 12–18 months does not affect gut microbiome diversity and composition over time. To our knowledge, this is the first study to report the effect of lactoferrin on infant gut microbiome composition over time and helps elucidate its impact on infant health and its therapeutic potential.
L-glutamine sensitizes Gram-positive-resistant bacteria to gentamicin killing
Authors: Fan Lvyuan , Pan Zhiyu , Zhong Yilin , Guo Juan , Liao Xu , Pang Rui , Xu Qingqiang , Ye Guozhu , Su Yubin 
Published: October 2023

ABSTRACT

Because of the stubborn resistance to antibiotics, treating clinically resistant bacteria is a tricky business. Although considerable attention has been devoted to preventing and treating infections from drug-resistant bacteria, few studies are available on combining metabolites and antibiotics to combat methicillin-resistant
Staphylococcus aureus
(MRSA). This study found that exogenous L-glutamine potentiated aminoglycoside (gentamicin)-mediated killing efficacy in a dose- and time-dependent manner in MRSA (USA300 cell line) and other Gram-positive-resistant bacteria including MRSA 252,
Listeria monocytogenes
, and
Corynebacterium diphtheriae
. L-glutamine promoted the uptake of gentamicin through increasing the membrane permeability and was correlated with disrupted pH gradient. Furthermore, L-glutamine decreased intracellular reactive oxygen species by glutathione, which also increased USA300 sensitivity to gentamicin. We also demonstrated that combined treatment with gentamicin and L-glutamine enhanced the survival of MRSA-infected mice. In conclusion, we developed a promising therapeutic strategy for treating Gram-positive-resistant bacterial infections.

IMPORTANCE

Methicillin-resistant
Staphylococcus aureus
(MRSA) infection severely threatens human health due to high morbidity and mortality; it is urgent to develop novel strategies to tackle this problem. Metabolites belong to antibiotic adjuvants which improve the effect of antibiotics. Despite reports of L-glutamine being applied in antibiotic adjuvant for Gram-negative bacteria, how L-glutamine affects antibiotics against Gram-positive-resistant bacteria is still unclear. In this study, L-glutamine increases the antibacterial effect of gentamicin on MRSA, and it links to membrane permeability and pH gradient (ΔpH), resulting in uptake of more gentamicin. Of great interest, reduced reactive oxygen species (ROS) by glutathione was found under L-glutamine treatment; USA300 becomes sensitive again to gentamicin. This study not only offers deep understanding on ΔpH and ROS on bacterial resistance but also provides potential treatment solutions for targeting MRSA infection.