Colonization resistance: metabolic warfare as a strategy against pathogenic Enterobacteriaceae

Abstract Background Despite their elevated risk for morbidity and mortality from infections, the microbiota of older adults remain understudied. While colonization resistance from resident microflora is a promising means to prevent infections, little is known about pathogenicity reservoirs and colonization resistance in this vulnerable population. Here we study the skin, oral, and gut microbiome dynamics of older adults in both community and Skilled Nursing Facility (SNF) settings, investigating relationships between age, frailty, environment, microbiota, and pathogenicity reservoirs. Methods We conducted a longitudinal metagenome survey of 47 adults age 65+ years of age; 22 residents of 3 different SNFs and 25 community dwelling individuals. We performed metagenomic whole genome shotgun sequencing on stool, oral, and skin samples from 8 sites, 1421 total. To correlate clinical and behavioral variables, we measured frailty, collected medical records, and interviewed participants on diet and lifestyle. We also draw comparisons with previous younger cohorts. Results • Compared to younger adults, the skin microbiota of older adults was characterized by ◦ High heterogeneity ◦ Decreased stability over time, suggesting increased susceptibility to colonization and pathogenicity ◦ Compositional differences including significantly lower levels of Cutibacterium acnes, with reciprocal increases in Staphylococci, Corynebacteria, and Malassezia • In older adults, Frailty (Rockwood) was found to have linear correlation with relative abundance of species relevant to infection risk including acnes, staphylococci, streptococci, E. coli, Akkermansia mucinophila, and Enterococcus faecalis. • The skin, oral, and gut microbiota of SNF residents had substantially elevated virulence factor and antibiotic resistance genes. Conclusion To the best of our knowledge, this is largest report to date of the skin metagenome in older adults. We demonstrate distinct and significant differences between cohorts with clinically relevant implications. We believe these results may inform infection control and prevention by increasing our understanding of colonization resistance and pathogenicity reservoirs, as well as advance our knowledge of the relationship between aging, the microbiome, and infections. Disclosures All Authors: No reported disclosures

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Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease

mBio ◽

10.1128/mbio.00321-19 ◽

2019 ◽

Vol 10 (2) ◽

Cited By ~ 19

Author(s):

Gajender Aleti ◽

Jonathon L. Baker ◽

Xiaoyu Tang ◽

Ruth Alvarez ◽

Márcia Dinis ◽

...

Keyword(s):

Dental Caries ◽

Small Molecules ◽

Gene Clusters ◽

Signaling Molecules ◽

Oral Bacteria ◽

Oral Microbiome ◽

Communication Media ◽

Biosynthetic Gene ◽

Colonization Resistance ◽

Biosynthetic Gene Clusters

ABSTRACT Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world’s most common chronic diseases. IMPORTANCE The healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world’s most common and costly chronic infectious diseases and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome and how it devolves in the case of two prominent diseases.

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Klebsiella oxytoca causes colonization resistance against multidrug-resistant K. pneumoniae in the gut via cooperative carbohydrate competition

Cell Host & Microbe ◽

10.1016/j.chom.2021.09.003 ◽

2021 ◽

Author(s):

Lisa Osbelt ◽

Marie Wende ◽

Éva Almási ◽

Elisabeth Derksen ◽

Uthayakumar Muthukumarasamy ◽

...

Keyword(s):

Klebsiella Oxytoca ◽

Multidrug Resistant ◽

Colonization Resistance

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Colonization Resistance

Gastrointestinal Microbiology ◽

10.1007/978-1-4757-0322-1_13 ◽

1997 ◽

pp. 501-536 ◽

Cited By ~ 14

Author(s):

Rial D. Rolfe

Keyword(s):

Colonization Resistance

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Streptomycin-Induced Inflammation Enhances Escherichia coli Gut Colonization Through Nitrate Respiration

mBio ◽

10.1128/mbio.00430-13 ◽

2013 ◽

Vol 4 (4) ◽

Cited By ~ 92

Author(s):

Alanna M. Spees ◽

Tamding Wangdi ◽

Christopher A. Lopez ◽

Dawn D. Kingsbury ◽

Mariana N. Xavier ◽

...

Keyword(s):

Escherichia Coli ◽

Microbial Community ◽

Intestinal Inflammation ◽

Anaerobic Bacteria ◽

Nitrate Respiration ◽

Colonization Resistance ◽

Content Type ◽

E Coli ◽

Gut Colonization ◽

Facultative Anaerobic Bacteria

ABSTRACTTreatment with streptomycin enhances the growth of human commensalEscherichia coliisolates in the mouse intestine, suggesting that the resident microbial community (microbiota) can inhibit the growth of invading microbes, a phenomenon known as “colonization resistance.” However, the precise mechanisms by which streptomycin treatment lowers colonization resistance remain obscure. Here we show that streptomycin treatment rendered mice more susceptible to the development of chemically induced colitis, raising the possibility that the antibiotic might lower colonization resistance by changing mucosal immune responses rather than by preventing microbe-microbe interactions. Investigation of the underlying mechanism revealed a mild inflammatory infiltrate in the cecal mucosa of streptomycin-treated mice, which was accompanied by elevated expression ofNos2, the gene that encodes inducible nitric oxide synthase. In turn, this inflammatory response enhanced the luminal growth ofE. coliby nitrate respiration in aNos2-dependent fashion. These data identify low-level intestinal inflammation as one of the factors responsible for the loss of resistance toE. colicolonization after streptomycin treatment.IMPORTANCEOur intestine is host to a complex microbial community that confers benefits by educating the immune system and providing niche protection. Perturbation of intestinal communities by streptomycin treatment lowers “colonization resistance” through unknown mechanisms. Here we show that streptomycin increases the inflammatory tone of the intestinal mucosa, thereby making the bowel more susceptible to dextran sulfate sodium treatment and boosting theNos2-dependent growth of commensalEscherichia coliby nitrate respiration. These data point to the generation of alternative electron acceptors as a by-product of the inflammatory host response as an important factor responsible for lowering resistance to colonization by facultative anaerobic bacteria such asE. coli.

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Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells

Mucosal Immunology ◽

10.1038/mi.2014.94 ◽

2014 ◽

Vol 8 (3) ◽

pp. 618-626 ◽

Cited By ~ 55

Author(s):

J Chen ◽

A Waddell ◽

Y-D Lin ◽

M T Cantorna

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Citrobacter Rodentium ◽

Colonization Resistance

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The condition of colonization resistance in surgical patientsearly after the surgery

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2007-2-60-64 ◽

2007 ◽

Vol 6 (2) ◽

pp. 60-64

Author(s):

A. B. Chebotar’ ◽

M. V. Choubik ◽

Ye. P. Krasnozhenov ◽

G. Ts. Dambayev

Keyword(s):

Selective Decontamination ◽

Surgical Patients ◽

Hospital Infections ◽

Colonization Resistance ◽

Normal Microflora ◽

Complex Approach ◽

Immunological Mechanisms ◽

Focus Localization ◽

Special Diets ◽

Main Components

We have examined one of the main components of the mechanism of purulent-inflammation complications in surgical patients. It is normal microflora which reflects the condition of colonization resistance of the organism which is a leading mechanism of opposition to hospital infections. We have established changes of microflora of different biotopes of the organism in dependence on pathologic focus localization and of the period after the surgery. Complex approach to the investigation of colonization resistance allowed to discover not only dysbiotic changes but disturbances of some immunological mechanisms of total and local anti- infectious protection in surgical patients. It is desirable to combine selective decontamination with taking drugs which normalize indigenous micro-flora of the host (special diets, growth stimulators of normal microflora representatives, eubiotics) and immune-stimulating therapy.

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Separation of Donor and Recipient Microbial Diversity Allows Determination of Taxonomic and Functional Features of Gut Microbiota Restructuring following Fecal Transplantation

mSystems ◽

10.1128/msystems.00811-21 ◽

2021 ◽

Author(s):

Evgenii I. Olekhnovich ◽

Artem B. Ivanov ◽

Vladimir I. Ulyantsev ◽

Elena N. Ilina

Keyword(s):

Gut Microbiota ◽

Antibiotic Resistance Genes ◽

Host Immunity ◽

Third Party ◽

Colonization Resistance ◽

Fecal Transplantation ◽

Antimicrobial Substances ◽

Functional Features ◽

Microbiota Structure

We assumed that the enrichment of successful gut microbes by lantibiotic/antibiotic resistance genes can be related to gut microbiota colonization resistance by third-party microbe phenomena and resistance to bacterium-derived or host-derived antimicrobial substances. According to this assumption, competition between the donor-derived and recipient-derived microbes as well as host immunity may play a key role in the FMT-related colonization and redistribution of recipient gut microbiota structure.

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