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Author Victor Nizet

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An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37

Piotr Kolesiński, Kuei-Chen Wang, Yujiro Hirose, Victor Nizet, Partho Ghosh,

<h4>ABSTRACT</h4> Surface-associated, coiled-coil M proteins of Streptococcus pyogenes (Strep A) disable human immunity through interaction with select proteins. However, coiled coils lack features typical of protein-protein interaction sites, and it is therefore challenging to understand how M proteins achieve specific binding, for example, with the human antimicrobial peptide LL-37, which ... Read more >>

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Human Milk Oligosaccharides Reduce Murine Group B Streptococcus Vaginal Colonization with Minimal Impact on the Vaginal Microbiota.

Marlyd E Mejia, Samantha Ottinger, Alison Vrbanac, Priyanka Babu, Jacob J Zulk, David Moorshead, Lars Bode, Victor Nizet, Kathryn A Patras,

Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy, and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. ... Read more >>

mSphere (mSphere)
[2022, :e0088521]

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Bicarbonate modulates delafloxacin activity against MDR Staphylococcus aureus and Pseudomonas aeruginosa.

Mische Holland, Elisabet Bjanes, Victor Nizet, Nicholas Dillon,

<h4>Objectives</h4>To investigate the utility of recently approved delafloxacin and other fluoroquinolones against leading MDR bacterial pathogens under physiologically relevant conditions.<h4>Methods</h4>MIC and MBC assays were conducted for MDR strains of Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae in the standard antibiotic susceptibility testing medium CAMHB, amended Roswell-Park Memorial Institute ... Read more >>

J Antimicrob Chemother (The Journal of antimicrobial chemotherapy)
[2021, :]

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Design of M protein immunogens to elicit broadly reactive antibodies against Streptococcus pyogenes

Kuei-Chen Wang, Victor Nizet, Partho Ghosh,

M proteins of the widespread and potentially deadly bacterial pathogen Streptococcus pyogenes (Strep A) are immunodominant targets of opsonizing antibodies. However, the antigenic sequence variability of the M protein into >220 M types has limited its utility as a vaccine immunogen, as antibody recognition is usually type-specific. At present no ... Read more >>

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Vascular proteome responses precede organ dysfunction in sepsis

James Sorrentino, Gregory Golden, Claire Morris, Chelsea Painter, Victor Nizet, Alexandre Rosa Campos, Jeffrey Smith, Christofer Karlsson, Johan Malmström, Nathan Lewis, Jeffrey Esko, Alejandro Gómez Toledo,

Vascular dysfunction and organ failure are two distinct, albeit highly interconnected clinical outcomes linked to morbidity and mortality in human sepsis. The mechanisms driving vascular and parenchymal damage are dynamic and display significant molecular crosstalk between organs and tissues. Therefore, assessing their individual contribution to disease progression is technically challenging. ... Read more >>

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Uremic serum damages endothelium by provoking excessive neutrophil extracellular trap formation.

Hoi Woul Lee, Victor Nizet, Jung Nam An, Hyung Seok Lee, Young Rim Song, Sung Gyun Kim, Jwa-Kyung Kim,

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced ... Read more >>

Sci Rep (Scientific reports)
[2021, 11(1):21439]

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Ticagrelor Increases Platelet-Mediated Staphylococcus aureus Killing, Resulting in Clearance of Bacteremia.

Erlinda R Ulloa, Satoshi Uchiyama, Robert Gillespie, Victor Nizet, George Sakoulas,

Platelets are a critical immune defense against Staphylococcus aureus bloodstream infections. Staphylococcus aureus α-toxin is a virulence factor that decreases platelet viability and accelerates platelet clearance. It has been shown that ticagrelor blocks α-toxin-mediated platelet injury and resulting thrombocytopenia, protecting mice in a lethal S. aureus sepsis model. We now ... Read more >>

J Infect Dis (The Journal of infectious diseases)
[2021, 224(9):1566-1569]

Cited: 1 time

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Human milk oligosaccharides reduce murine group B Streptococcus vaginal colonization with minimal impact on the vaginal microbiota

Marlyd Mejia, Samantha Ottinger, Alison Vrbanac, Priyanka Babu, Jacob Zulk, David Moorshead, Lars Bode, Victor Nizet, Kathryn Patras,

<h4>ABSTRACT</h4> Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the ... Read more >>

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The S Protein of Group B Streptococcus Is a Critical Virulence Determinant That Impacts the Cell Surface Virulome.

Anaamika Campeau, Satoshi Uchiyama, Concepcion Sanchez, Consuelo Sauceda, Victor Nizet, David J Gonzalez,

Group B <i>Streptococcus</i> (GBS, <i>S. agalactiae</i>) is a human commensal and occasional pathogen that remains a leading cause of neonatal sepsis and meningitis with increasing disease burden in adult populations. Although programs for universal screening in pregnancy to guide intrapartum prophylaxis have reduced GBS invasive disease burden resulting from mother-to-newborn ... Read more >>

Front Microbiol (Frontiers in microbiology)
[2021, 12:729308]

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Editorial: Host-Pathogen Interactions During Pneumococcal Infection.

Masaya Yamaguchi, Yuki Kinjo, Victor Nizet,

Front Cell Infect Microbiol (Frontiers in cellular and infection microbiology)
[2021, 11:752959]

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Bacterial Membrane-Derived Vesicles Attenuate Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus.

Monika Kumaraswamy, Kamilla Wiull, Bishnu Joshi, George Sakoulas, Armin Kousha, Gustav Vaaje-Kolstad, Mona Johannessen, Kristin Hegstad, Victor Nizet, Fatemeh Askarian,

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) has evolved numerous antimicrobial resistance mechanisms and is identified as a serious public health threat by the World Health Organization and U.S. Centers for Disease Control and Prevention. The glycopeptide vancomycin (VAN) remains a cornerstone of therapy for severe MRSA infections despite increasing reports of therapeutic ... Read more >>

Microorganisms (Microorganisms)
[2021, 9(10):]

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Machine Learning of Bacterial Transcriptomes Reveals Responses Underlying Differential Antibiotic Susceptibility.

Anand V Sastry, Nicholas Dillon, Amitesh Anand, Saugat Poudel, Ying Hefner, Sibei Xu, Richard Szubin, Adam M Feist, Victor Nizet, Bernhard Palsson,

<i>In vitro</i> antibiotic susceptibility testing often fails to accurately predict <i>in vivo</i> drug efficacies, in part due to differences in the molecular composition between standardized bacteriologic media and physiological environments within the body. Here, we investigate the interrelationship between antibiotic susceptibility and medium composition in Escherichia coli K-12 MG1655 as ... Read more >>

mSphere (mSphere)
[2021, 6(4):e0044321]

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Immunobiology of the Classical Lancefield Group A Streptococcal Carbohydrate Antigen.

Nina J Gao, Ervin Rodas Lima, Victor Nizet,

Group A Streptococcus (GAS) is a preeminent human bacterial pathogen causing hundreds of millions of infections each year worldwide. In the clinical setting, the bacterium is easily identified by a rapid antigen test against the group A carbohydrate (GAC), a polysaccharide that comprises 30 to 50% of the GAS cell ... Read more >>

Infect Immun (Infection and immunity)
[2021, 89(12):e0029221]

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Streptolysins are the primary inflammasome activators in macrophages during Streptococcus pyogenes infection.

Johanna Richter, Mercedes M Monteleone, Amanda J Cork, Timothy C Barnett, Victor Nizet, Stephan Brouwer, Kate Schroder, Mark J Walker,

Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes an array of infectious diseases in humans. Accumulating clinical evidence suggests that proinflammatory interleukin (IL)-1β signaling plays an important role in GAS disease progression. The host regulates the production and secretion of IL-1β via the cytosolic inflammasome pathway. Activation ... Read more >>

Immunol Cell Biol (Immunology and cell biology)
[2021, 99(10):1040-1052]

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Heat shock protein 27 activity is linked to endothelial barrier recovery after proinflammatory GPCR-induced disruption.

Cara C Rada, Hilda Mejia-Pena, Neil J Grimsey, Isabel Canto Cordova, Joshua Olson, Jacob M Wozniak, David J Gonzalez, Victor Nizet, JoAnn Trejo,

[Figure: see text]. ... Read more >>

Sci Signal (Science signaling)
[2021, 14(698):eabc1044]

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Environmental conditions dictate differential evolution of vancomycin resistance in Staphylococcus aureus.

Henrique Machado, Yara Seif, George Sakoulas, Connor A Olson, Ying Hefner, Amitesh Anand, Ying Z Jones, Richard Szubin, Bernhard O Palsson, Victor Nizet, Adam M Feist,

While microbiological resistance to vancomycin in Staphylococcus aureus is rare, clinical vancomycin treatment failures are common, and methicillin-resistant S. aureus (MRSA) strains isolated from patients after prolonged vancomycin treatment failure remain susceptible. Adaptive laboratory evolution was utilized to uncover mutational mechanisms associated with MRSA vancomycin resistance in a physiological medium ... Read more >>

Commun Biol (Communications biology)
[2021, 4(1):793]

Cited: 1 time

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Uremic Serum Damages Endothelium by Provoking Excessive Neutrophil Extracellular Trap Formation

Hoi Woul Lee, Victor Nizet, Jung Nam An, Hyung Seok Lee, Young Rim Song, Sung Gyun Kim, Jwa-Kyung Kim,

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced ... Read more >>

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Hypoxia-Inducible Factor 1 Alpha Is Dispensable for Host Defense of Group B Streptococcus Colonization and Infection.

Gregory R Lum, Vicki Mercado, Diede van Ens, Victor Nizet, Jacqueline M Kimmey, Kathryn A Patras,

Group B Streptococcus (GBS) is a leading cause of neonatal morbidity and mortality, and the primary source of exposure is the maternal vagina. Intrapartum antibiotic prophylaxis for GBS-positive mothers has reduced the incidence of GBS early-onset disease, however, potential long-lasting influence of an antibiotic-altered neonatal microbiota, and the frequent clinical ... Read more >>

J Innate Immun (Journal of innate immunity)
[2021, 13(6):391-403]

Cited: 1 time

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Current Paradigms of Combination therapy in Methicillin-Resistant Staphylococcus aureus (MRSA) Bacteremia: Does it Work, Which Combination and For Which Patients?

Warren Rose, Michael Fantl, Matthew Geriak, Victor Nizet, George Sakoulas,

The last several years have seen an emergence of literature documenting the utility of combination antimicrobial therapy, particularly in the salvage of refractory MRSA bacteremia. Recent clinical data are shaping conundrums of which regimens may be more beneficial, which can be potentially harmful, and which subset of patients stand to ... Read more >>

Clin Infect Dis (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America)
[2021, :]

Cited: 3 times

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CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections

Araceli Perez-Lopez, Steven Silva, Nicholas Dillon, Stephanie Brandt, Romana Gerner, Michael Lee, Karine Melchior, Jiram Torres-Ruiz, Victor Sosa-Hernandez, Rodrigo Cervantes-Diaz, Alfredo Perez-Fragoso, Sandra Romero-Ramirez, Diana Gomez-Martin, Jose Maravillas-Montero, Sean-Paul Nuccio, Victor Nizet, Manuela Raffatellu,

<h4>Summary</h4> The mucosal chemokine CCL28 is highly upregulated during infection but its role in this context is not well understood. Utilizing Ccl28 -/- mice, we discovered that CCL28 promotes neutrophil recruitment to the infected mucosa. Neutrophils from these tissues expressed the CCL28 receptor CCR3, and CCR3 stimulation enhanced neutrophil antimicrobial ... Read more >>

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Repurposed drugs block toxin-driven platelet clearance by the hepatic Ashwell-Morell receptor to clear Staphylococcus aureus bacteremia.

Josh Sun, Satoshi Uchiyama, Joshua Olson, Yosuke Morodomi, Ingrid Cornax, Nao Ando, Yohei Kohno, May M T Kyaw, Bernice Aguilar, Nina M Haste, Sachiko Kanaji, Taisuke Kanaji, Warren E Rose, George Sakoulas, Jamey D Marth, Victor Nizet,

<i>Staphylococcus aureus</i> (SA) bloodstream infections cause high morbidity and mortality (20 to 30%) despite modern supportive care. In a human bacteremia cohort, we found that development of thrombocytopenia was correlated to increased mortality and increased α-toxin expression by the pathogen. Platelet-derived antibacterial peptides are important in bloodstream defense against SA, ... Read more >>

Sci Transl Med (Science translational medicine)
[2021, 13(586):]

Cited: 4 times

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Opportunistic Invasive Infection by Group A Streptococcus During Anti-Interleukin-6 Immunotherapy.

Shyra Wilde, Katherine L Olivares, Victor Nizet, Hal M Hoffman, Suhas Radhakrishna, Christopher N LaRock,

Invasive group A Streptococcus (GAS) in immunocompetent individuals is largely linked to hypervirulent strains. Congenital immunodeficiencies and those acquired from chronic disease or immunosuppressant drugs also increase risk of severe illness. We recovered GAS from the blood of a patient receiving a biologic inhibitor of interleukin 6 (IL-6). Growth of ... Read more >>

J Infect Dis (The Journal of infectious diseases)
[2021, 223(7):1260-1264]

Cited: 3 times

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Driving to Safety: CRISPR-Based Genetic Approaches to Reducing Antibiotic Resistance.

Ethan Bier, Victor Nizet,

Bacterial resistance to antibiotics has reached critical levels, skyrocketing in hospitals and the environment and posing a major threat to global public health. The complex and challenging problem of reducing antibiotic resistance (AR) requires a network of both societal and science-based solutions to preserve the most lifesaving pharmaceutical intervention known ... Read more >>

Trends Genet (Trends in genetics : TIG)
[2021, 37(8):745-757]

Cited: 1 time

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Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface.

Yujiro Hirose, Masaya Yamaguchi, Tomoko Sumitomo, Masanobu Nakata, Tomoki Hanada, Daisuke Okuzaki, Daisuke Motooka, Yasushi Mori, Hiroshi Kawasaki, Alison Coady, Satoshi Uchiyama, Masanobu Hiraoka, Raymond H Zurich, Masayuki Amagai, Victor Nizet, Shigetada Kawabata,

The arginine deiminase (ADI) pathway has been found in many kinds of bacteria and functions to supplement energy production and provide protection against acid stress. The Streptococcus pyogenes ADI pathway is upregulated upon exposure to various environmental stresses, including glucose starvation. However, there are several unclear points about the advantages ... Read more >>

Cell Rep (Cell reports)
[2021, 34(13):108924]

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More than a Pore: Nonlytic Antimicrobial Functions of Complement and Bacterial Strategies for Evasion.

Elisabet Bjanes, Victor Nizet,

The complement system is an evolutionarily ancient defense mechanism against foreign substances. Consisting of three proteolytic activation pathways, complement converges on a common effector cascade terminating in the formation of a lytic pore on the target surface. The classical and lectin pathways are initiated by pattern recognition molecules binding to ... Read more >>

Microbiol Mol Biol Rev (Microbiology and molecular biology reviews : MMBR)
[2021, 85(1):]

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