Biology subjects

Green, S. I.

Publications and source records attributed to Green, S. I..

5 recordsLinked to original sources

bioRxiv2026

Genomic epidemiology of Ukraine conflict-associated Klebsiella pneumoniae reveals the emergence of a high-risk clone with a hybrid virulence-resistance plasmid vulnerable to lytic phages

As antimicrobial resistance continues to rise and the development of new antimicrobials lags, we face an urgent threat where routine infections could become life-threatening. Armed conflicts, like Russias war on Ukraine, intensify this crisis by accelerating the emergence and spread of resistant organisms across regions and borders. Phage Support Ukraine (Phage Sp UKR) is a collaborative effort to provide phages targeting circulating pathogens in Ukraine for delivery of personalized phage therapies. Within this context, we received multidrug-resistant bacterial isolates belonging to a number of different species. We here focus on Klebsiella pneumoniae, the most concerning pathogen with regard to prevalence, virulence and antibiotic resistance. Among the K. pneumoniae isolates, we identified sequence types (ST) 39, 101, 147, 307 and 395, as well as a predominating clonal group--CG10146 (ST23 KL57), first detected in Moscow--carrying a hybrid virulence-resistance plasmid encoding NDM-1 and aerobactin. Over two years (2023-2025), this clonal group expanded and acquired pan-resistance. When tested in virulence assays, only one isolate (ST395) displayed hypervirulence in a Galleria mellonella though not in a mouse infection model. Several phages isolated from Ukrainian sewage were able to lyse these K. pneumoniae strains, including strains obtained from soldiers displaced in Belgium, Germany, and Latvia. Bacterial resistance was observed during in vitro testing. However, some phage-resistant isolates had mutations in virulence factors, including one that completely lost its hybrid plasmid, resulting in restored antibiotic susceptibility. Strategies like Phage Sp UKR are essential to prevent the selection, persistence, and global spread of these MDR clones.

microbiology↗

bioRxiv2023

Understanding the bacterial imbalance in Hidradenitis Suppurativa patients: Insights into microbial community shifts and colonization by opportunistic pathogens

Patients suffering from hidradenitis suppurativa (HS) develop painful skin lesions, significantly decreasing their quality of life. This chronic disease is triggered by plugged hair follicles resulting in an aberrant immune response, skin microbiome imbalance and secondary bacterial colonization. As a result, a diversity of treatment options are currently applied, including antibiotics, biologicals like adalimumab and surgery, which often provide only short-term relief. Alternative strategies, like phage therapy, have been proposed but identification of the target bacterium is key. Therefore, a spatial and longitudinal analysis was performed on skin swabs of lesions from 39 HS patients and 18 healthy controls, leading to a total collection of 108 lesional samples and 35 control samples at different time points and locations throughout the body. Samples were subjected to 16S rRNA community analysis, as well as bacterial isolation using aerobic and anaerobic culturing in combination with MALDI-TOF. Our data demonstrate that the bacterial community present in lesions of patients with HS is out of balance compared to healthy individuals, in which the niche of Staphylococcus and Corynebacterium is taken over by Escherichia-Shigella. Overall, three bacterial community profiles of HS lesions and one of healthy individuals could be distinguished. Although the overall bacterial composition was not associated with the disease severity defined by the Hurley classification system, lesions often become colonized with opportunistic pathogens including Staphylococcus aureus and Pseudomonas aeruginosa at increasing disease severities. Furthermore, patients with a concurrent IBD diagnosis did not reveal a significantly different bacterial skin community.

microbiology↗

bioRxiv2023

Hidradenitis suppurativa patients exhibit a distinctive and highly individualized skin virome

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by recurring painful skin lesions. Despite ongoing research, the exact cause underlying the initiation and progression of disease remains unknown. While prior research has linked the skin microbiota to HS pathology, the role of viruses has remained unexplored. To investigate the skin virota, metagenomic sequencing of viral particles was performed on 144 skin samples from 57 individuals (39 HS patients and 18 controls). It was found that the virome is not only linked to BMI, but also to the presence and severity of HS, marking a diverging viral profile in the progression of disease. Despite no differences in alpha-diversity, HS patients exhibited a significantly higher beta-diversity compared to healthy controls, indicating a more personalized virome with reduced viral sharing among patients. We identified distinct groups of commonly shared phages, referred to as the core phageome, associated with either healthy controls or patients. Healthy controls displayed a higher abundance of two core Caudoviricetes phages predicted to infect Corynebacterium and Staphylococcus, comprising normal skin commensals. In contrast, HS patients carried previously uncharacterized phages that were more prevalent in advanced stages of the disease, which likely infect Peptoniphilus and Finegoldia, known HS-associated pathogens. Interestingly, genes involved in superinfection exclusion and antibiotic resistance could be found in phage genomes of healthy controls and HS patients, respectively. In conclusion, we report the existence of distinct core phages that may have clinical relevance in HS pathology by influencing skin bacteria through mechanisms such as superinfection exclusion and antibiotic resistance.

microbiology↗

bioRxiv2020

Targeting of Mammalian Glycans Enhances Phage Predation in the Gastrointestinal Tract

The human mucosal surface consists of a eukaryotic epithelium, a prokaryotic microbiota, and a carbohydrate-rich interface that separates them. Bacteriophage parasitize the prokaryotes but are not known to associate with eukaryotic cells. In the gastrointestinal tract, the interaction of these two domains influences the health of the host, especially colonization with invasive pathobionts. Antibiotics may be used but they also kill protective commensals and lack the physio-chemical properties to be specifically and optimally active in this complex milieu. Here, we report a novel phage whose lytic cycle is enhanced in intestinal environments. The enhanced activity is encoded in its tail fiber gene, whose protein product binds human heparan sulfated proteoglycans and localizes the phage to the epithelial cell surface, thereby positioning it near its bacterial host, a type of locational targeting mechanism. This finding offers the prospect of developing epithelial-targeting phage to selectively remove invasive pathobiont species from mucosal surfaces. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/212829v2_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@13219f6org.highwire.dtl.DTLVardef@469d7borg.highwire.dtl.DTLVardef@d31e0org.highwire.dtl.DTLVardef@458e14_HPS_FORMAT_FIGEXP M_FIG C_FIG Model showing (1) mucins from the intestinal mucus layer inhibit phage infection, (2) phage ES17 can bind to mucin and utilize other intestinal glycans as a receptor to infect and kill mucus-coated bacteria, and (3) phages like ES17 can be utilized to coat the intestinal epithelium by binding heparan sulfate glycans to protect from invasive pathogen infection.

microbiology↗

bioRxiv2020

Phage-Antibiotic Synergy Is Driven By A Unique Combination Of Antibacterial Mechanism Of Action And Stoichiometry

The continued rise in antibiotic resistance is precipitating a medical crisis. Bacteriophage (phage) has been hailed as one possible therapeutic option to augment the efficacy of antibiotics. However, only a handful of studies have addressed the synergistic relationship between phage and antibiotics. Here, we report a comprehensive analysis of phage-antibiotic interaction that evaluates synergism, additivism, and antagonism for all classes of antibiotics across clinically achievable stoichiometries. We combined an optically-based real-time microtiter plate readout with a matrix-like heatmap of treatment potencies to measure phage and antibiotic synergy (PAS), a process we term synography. Phage-antibiotic synography was performed against a pandemic drug-resistant clonal group of E. coli (ExPEC) with antibiotic levels blanketing the minimum inhibitor concentration (MIC) across seven orders of viral titers. Our results suggest that, under certain conditions, phages provide an adjuvating effect by lowering the MIC for drug-resistant strains. Furthermore, synergistic and antagonistic interactions are highly dependent on the mechanism of bacterial inhibition by the class of antibiotic paired to the phage, and when synergism is observed, it suppresses the emergence of resistant cells. Host conditions that simulate the infection environment, including serum and urine, suppress PAS in a bacterial growth-dependent manner. Lastly, phage burst size seems to be a significant driver of synergism. Collectively, this data suggests lytic phages can resuscitate an ineffective antibiotic for previously resistant bacteria, while also synergize with antibiotics in a class-dependent manner, processes that may be dampened by lower bacterial growth rates found in host environments. Significance StatementBacteriophage (phage) therapy is a promising approach to combat the rise of multi-drug resistant bacteria. Currently, the preferred clinical modality is to pair phage with an antibiotic, a practice thought to improve efficacy. However, antagonism between phage and antibiotics has been reported, the choice of phage and antibiotic is not often empirically determined, and the effect of the host factors on the effectiveness is unknown. Here, we interrogate phage-antibiotic interactions across antibiotics with different mechanisms of action. Our results suggest that phage can lower the working MIC for bacterial strains already resistant to the antibiotic, is dependent on the antibiotic class and stoichiometry of the pairing, and is dramatically influenced by the host microenvironment.

microbiology↗