EL PAPEL DEL MICROBIOMA DE LA LECHE MATERNA HUMANA EN LA MODULACION DEL SISTEMA INMUNE DEL NEONATO

Human breast milk is an optimal source of nutrition  for  infants,  since  it  is  a  food  rich  in  bioactive  substances  such  as  carbohy-drates,  lipids,  vitamins,  among  others,  as  well as an abundance of microorganisms, oligosaccharides,   immunoglobulins   and   others,  that  you  are  right  Development  of  information and healthy intestinal microbio-ta. Based on this, formerly it was believed that human breast milk was a body fluid, the  presence  of  bacteria  in  this  genera-tion debate about the scientific community, about the possible source and function of this  microbiota  in  the  health  and  modu-lation  of  the  immune  system  of  the  baby.  Therefore,  thanks  to  the  development  of  bioinformatic tools such as metagenomics, the  study  of  microorganisms  in  the  world,  in natural environments, in unexplored or-ganisms  and  places  has  been  achieved.  This type of tools allows, therefore, to ob-tain  DNA  samples  of  the  rRNA  16s  gene  quickly  and  obtain  results  about  the  com-plete  composition  of  the  sample  in  terms  of  microorganisms.  For  this  reason,  the  main  objective  of  this  review  is  to  collect  information in order to demonstrate the im-portance of human breast milk as the food that allows the modulation of the system in babies throughout their lives thanks to the microbiome present in this and other data of great interestLa leche  materna  humana  es  una  fuente  óptima  de  nutrición  para  los  bebés,  dado  que es un alimento rico en sustancias bio-activas  como  carbohidratos,  lípidos,  vita-minas, entre otros, así como una abundan-cia  de  microorganismos,  oligosacáridos,  inmunoglobulinas  y  demás,  que  permiten  un  correcto  desarrollo  del  infante  y  el  es-tablecimiento  de  una  microbiota  intestinal  sana. Con base en esto, antiguamente se creía  que  la  leche  materna  humana  era  un fluido corporal estéril, por lo que la pre-sencia de bacterias en esta generó debate entre  la  comunidad  científica,  acerca  de cuál era el posible origen y función de esta microbiota  en  la  salud  y  modulación  del  sistema  inmune  del  bebé.  Por  ende,  gra-cias  al  desarrollo  de  herramientas  bioin-formáticas  como  la  metagenómica,  se  ha  logrado  el  estudio  de  microorganismos  en  el  mundo,  en  ambientes  naturales,  en  organismos  y  lugares  inexplorados.  Este  tipo  de  herramientas  permite,  por  tanto,  obtener muestras de ADN del gen 16s del ARNr  de  forma  rápida  y  obtener  resulta-dos  acerca  de  la  composición  completa  de  la  muestra  en  cuanto  a  microorganis-mos.  Por  esta  razón,  el  principal  objetivo  de  esta  revisión  es  recopilar  información  con el fin de demostrar la importancia de la leche materna humana como alimento que permite la modulación del sistema inmune de los bebés a lo largo de su vida gracias al microbioma presente en esta y otros da-tos de gran interé

FOXM1 drives proximal tubule proliferation during repair from acute ischemic kidney injury

The proximal tubule has a remarkable capacity for repair after acute injury, but the cellular lineage and molecular mechanisms underlying this repair response are incompletely understood. Here, we developed a Kim1-GFPCreERt2 knockin mouse line (Kim1-GCE) in order to perform genetic lineage tracing of dedifferentiated cells while measuring the cellular transcriptome of proximal tubule during repair. Acutely injured genetically labeled clones coexpressed KIM1, VIMENTIN, SOX9, and KI67, indicating a dedifferentiated and proliferative state. Clonal analysis revealed clonal expansion of Kim1+ cells, indicating that acutely injured, dedifferentiated proximal tubule cells, rather than fixed tubular progenitor cells, account for repair. Translational profiling during injury and repair revealed signatures of both successful and unsuccessful maladaptive repair. The transcription factor Foxm1 was induced early in injury, was required for epithelial proliferation in vitro, and was dependent on epidermal growth factor receptor (EGFR) stimulation. In conclusion, dedifferentiated proximal tubule cells effect proximal tubule repair, and we reveal an EGFR/FOXM1-dependent signaling pathway that drives proliferative repair after injury

Antimicrobial sensing coupled with cell membrane remodeling mediates antibiotic resistance and virulence in Enterococcus faecalis.

Bacteria have developed several evolutionary strategies to protect their cell membranes (CMs) from the attack of antibiotics and antimicrobial peptides (AMPs) produced by the innate immune system, including remodeling of phospholipid content and localization. Multidrug-resistant Enterococcus faecalis, an opportunistic human pathogen, evolves resistance to the lipopeptide daptomycin and AMPs by diverting the antibiotic away from critical septal targets using CM anionic phospholipid redistribution. The LiaFSR stress response system regulates this CM remodeling via the LiaR response regulator by a previously unknown mechanism. Here, we characterize a LiaR-regulated protein, LiaX, that senses daptomycin or AMPs and triggers protective CM remodeling. LiaX is surface exposed, and in daptomycin-resistant clinical strains, both LiaX and the N-terminal domain alone are released into the extracellular milieu. The N-terminal domain of LiaX binds daptomycin and AMPs (such as human LL-37) and functions as an extracellular sentinel that activates the cell envelope stress response. The C-terminal domain of LiaX plays a role in inhibiting the LiaFSR system, and when this domain is absent, it leads to activation of anionic phospholipid redistribution. Strains that exhibit LiaX-mediated CM remodeling and AMP resistance show enhanced virulence in the Caenorhabditis elegans model, an effect that is abolished in animals lacking an innate immune pathway crucial for producing AMPs. In conclusion, we report a mechanism of antibiotic and AMP resistance that couples bacterial stress sensing to major changes in CM architecture, ultimately also affecting host-pathogen interactions

Genomic and SNP Analyses Demonstrate a Distant Separation of the Hospital and Community-Associated Clades of Enterococcus faecium

Recent studies have pointed to the existence of two subpopulations of Enterococcus faecium, one containing primarily commensal/community-associated (CA) strains and one that contains most clinical or hospital-associated (HA) strains, including those classified by multi-locus sequence typing (MLST) as belonging to the CC17 group. The HA subpopulation more frequently has IS16, pathogenicity island(s), and plasmids or genes associated with antibiotic resistance, colonization, and/or virulence. Supporting the two clades concept, we previously found a 3–10% difference between four genes from HA-clade strains vs. CA-clade strains, including 5% difference between pbp5-R of ampicillin-resistant, HA strains and pbp5-S of ampicillin-sensitive, CA strains. To further investigate the core genome of these subpopulations, we studied 100 genes from 21 E. faecium genome sequences; our analyses of concatenated sequences, SNPs, and individual genes all identified two distinct groups. With the concatenated sequence, HA-clade strains differed by 0–1% from one another while CA clade strains differed from each other by 0–1.1%, with 3.5–4.2% difference between the two clades. While many strains had a few genes that grouped in one clade with most of their genes in the other clade, one strain had 28% of its genes in the CA clade and 72% in the HA clade, consistent with the predicted role of recombination in the evolution of E. faecium. Using estimates for Escherichia coli, molecular clock calculations using sSNP analysis indicate that these two clades may have diverged ≥1 million years ago or, using the higher mutation rate for Bacillus anthracis, ∼300,000 years ago. These data confirm the existence of two clades of E. faecium and show that the differences between the HA and CA clades occur at the core genomic level and long preceded the modern antibiotic era

Accessory Genomes Drive Independent Spread of Carbapenem- Resistant Klebsiella pneumoniae Clonal Groups 258 and 307 in Houston, TX

Carbapenem-resistant Klebsiella pneumoniae (CRKp) is an urgent public health threat. Worldwide dissemination of CRKp has been largely attributed to clonal group (CG) 258. However, recent evidence indicates the global emergence of a CRKp CG307 lineage. Houston, TX, is the first large city in the United States with detected cocirculation of both CRKp CG307 and CG258. We sought to characterize the genomic and clinical factors contributing to the parallel endemic spread of CG258 and CG307. CRKp isolates were collected as part of the prospective, Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacterales 2 (CRACKLE-2) study. Hybrid short-read and long-read genome assemblies were generated from 119 CRKp isolates (95 originated from Houston hospitals). A comprehensive characterization of phylogenies, gene transfer, and plasmid content with pan-genome analysis was performed on all CRKp isolates. Plasmid mating experiments were performed with CG307 and CG258 isolates of interest. Dissection of the accessory genomes suggested independent evolution and limited horizontal gene transfer between CG307 and CG258 lineages. CG307 contained a diverse repertoire of mobile genetic elements, which were shared with other non-CG258 K. pneumoniae isolates. Three unique clades of Houston CG307 isolates clustered distinctly from other global CG307 isolates, indicating potential selective adaptation of particular CG307 lineages to their respective geographical niches. CG307 strains were often isolated from the urine of hospitalized patients, likely serving as important reservoirs for genes encoding carbapenemases and extendedspectrum b-lactamases. Our findings suggest parallel cocirculation of high-risk lineages with potentially divergent evolution

Photodynamic and Antibiotic Therapy Impair the Pathogenesis of Enterococcus faecium in a Whole Animal Insect Model

Enterococcus faecium has emerged as one of the most important pathogens in healthcare-associated infections worldwide due to its intrinsic and acquired resistance to many antibiotics, including vancomycin. Antimicrobial photodynamic therapy (aPDT) is an alternative therapeutic platform that is currently under investigation for the control and treatment of infections. PDT is based on the use of photoactive dye molecules, widely known as photosensitizer (PS). PS, upon irradiation with visible light, produces reactive oxygen species that can destroy lipids and proteins causing cell death. We employed Galleria mellonella (the greater wax moth) caterpillar fatally infected with E. faecium to develop an invertebrate host model system that can be used to study the antimicrobial PDT (alone or combined with antibiotics). In the establishment of infection by E. faecium in G. mellonella, we found that the G. mellonella death rate was dependent on the number of bacterial cells injected into the insect hemocoel and all E. faecium strains tested were capable of infecting and killing G. mellonella. Antibiotic treatment with ampicillin, gentamicin or the combination of ampicillin and gentamicin prolonged caterpillar survival infected by E. faecium (P = 0.0003, P = 0.0001 and P = 0.0001, respectively). In the study of antimicrobial PDT, we verified that methylene blue (MB) injected into the insect followed by whole body illumination prolonged the caterpillar survival (P = 0.0192). Interestingly, combination therapy of larvae infected with vancomycin-resistant E. faecium, with antimicrobial PDT followed by vancomycin, significantly prolonged the survival of the caterpillars when compared to either antimicrobial PDT (P = 0.0095) or vancomycin treatment alone (P = 0.0025), suggesting that the aPDT made the vancomycin resistant E. faecium strain more susceptible to vancomycin action. In summary, G. mellonella provides an invertebrate model host to study the antimicrobial PDT and to explore combinatorial aPDT-based treatments