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Innate lymphoid cells (ILCs) are tuned to quickly respond to and amplify tissue-specific signals. Work of three independent groups in Nature uncovers a novel mode of inflammatory communication between ILC2s and neurons at mucosal surfaces.
Yang Z, Maciejowski J, de Lange T
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Nuclear Envelope Rupture Is Enhanced by Loss of p53 or Rb
MOLECULAR CANCER RESEARCH 2017 NOV; 15(11):1579-1586
The mammalian nuclear envelope (NE) forms a stable physical barrier between the nucleus and the cytoplasm, normally breaking down only during mitosis. However, spontaneous transient NE rupture in interphase can occur when NE integrity is compromised, such as when the nucleus experiences mechanical stress. For instance, deficiencies in the nuclear lamins and their associated proteins can cause NE rupture that is promoted by forces exerted by actin filaments. NE rupture can allow cytoplasmic nucleases to access chromatin, potentially compromising genome integrity. Importantly, spontaneous NE rupture was noted in several human cancer cell lines, but the cause of this defect is not known. Here, we investigated the mechanistic contributions of two major tumor suppressors, p53 (TP53) and Rb (RB1), to the repression of NE rupture. NE rupture was induced in normal human epithelial RPE-1 cells upon impairment of either Rb or p53 achieved by shRNA knockdown and CRISPR/Cas9 gene editing. NE rupture did not involve diminished expression of NE components or greater cell motility. However, cells that underwent NE rupture displayed a larger nuclear projection area. In conclusion, the data indicate that NE rupture in cancer cells is likely due to loss of either the Rb or the p53 pathway. (C)2017 AACR.
Barandun J, Chaker-Margot M, Hunziker M, Molloy KR, Chait BT, Klinge S
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The complete structure of the small-subunit processome
NATURE STRUCTURAL & MOLECULAR BIOLOGY 2017 NOV; 24(11):944-953
The small-subunit processome represents the earliest stable precursor of the eukaryotic small ribosomal subunit. Here we present the cryo-EM structure of the Saccharomyces cerevisiae small-subunit processome at an overall resolution of 3.8 angstrom, which provides an essentially complete near-atomic model of this assembly. In this nucleolar superstructure, 51 ribosome-assembly factors and two RNAs encapsulate the 18S rRNA precursor and 15 ribosomal proteins in a state that precedes pre-rRNA cleavage at site A1. Extended flexible proteins are employed to connect distant sites in this particle. Molecular mimicry and steric hindrance, as well as protein-and RNA-mediated RNA remodeling, are used in a concerted fashion to prevent the premature formation of the central pseudoknot and its surrounding elements within the small ribosomal subunit.
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Smith C, Bartek R, Dominguez A, Buccilli A, Cooper SI, Henderson C, Rumerio P, West C, Arcaro D, Avetisyan A, Bose T, Gastler D, Rankin D, Richardson C, Rohlf J, Sulak L, Zou D, Benelli G, Cutts D, Garabedian A, Hakala J, Heintz U, Hogan JM, Kwok KHM, Laird E, Landsberg G, Mao Z, Narain M, Piperov S, Sagir S, Syarif R, Yu D, Band R, Brainerd C, Burns D, Sanchez MCD, Chertok M, Conway J, Conway R, Cox PT, Erbacher R, Flores C, Funk G, Gardner M, Ko W, Lander R, Mclean C, Mulhearn M, Pellett D, Pilot J, Shalhout S, Shi M, Smith J, Squires M, Stolp D, Tos K, Tripathi M, Wang Z, Bachtis M, Bravo C, Cousins R, Dasgupta A, Florent A, Hauser J, Ignatenko M, Mccoll N, Saltzberg D, Schnaible C, Valuev V, Bouvier E, Burt K, Clare R, Ellison J, Gary JW, Shirazi SMAG, Hanson G, Heilman J, Jandir P, Kennedy E, Lacroix F, Long OR, Negrete MO, Paneva MI, Shrinivas A, Si W, Wang L, Wei H, Wimpenny S, Yates BR, Branson JG, Cittolin S, Derdzinski M, Hashemi B, Holzner A, Klein D, Kole G, Krutelyov V, Letts J, Macneill I, Masciovecchio M, Olivito D, Padhi S, Pieri M, Sani M, Sharma V, Simon S, Tadel M, Vartak A, Wasserbaech S, Wood J, Wurthwein F, Yagil A, Della Porta GZ, Amin N, Bhandari R, Bradmiller-Feld J, Campagnari C, Dishaw A, Dutta V, Sevilla MF, George C, Golf F, Gouskos L, Gran J, Heller R, Incandela J, Mullin SD, Ovcharova A, Qu H, Richman J, Stuart D, Suarez I, Yoo J, Anderson D, Bendavid J, Bornheim A, Lawhorn JM, Newman HB, Nguyen T, Pena C, Spiropulu M, Vlimant JR, Xie S, Zhang Z, Zhu RY, Andrews MB, Ferguson T, Mudholkar T, Paulini M, Russ J, Sun M, Vogel H, Vorobiev I, Weinberg M, Cumalat JP, Ford WT, Jensen F, Johnson A, Krohn M, Leontsinis S, Mulholland T, Stenson K, Wagner SR, Alexander J, Chaves J, Chu J, Dittmer S, Mcdermott K, Mirman N, Patterson JR, Rinkevicius A, Ryd A, Skinnari L, Soffi L, Tan SM, Tao Z, Thom J, Tucker J, Wittich P, Zientek M, Abdullin S, Albrow M, Apollinari G, Apresyan A, Apyan A, Banerjee S, Bauerdick LAT, Beretvas A, Berryhill J, Bhat PC, Bolla G, Burkett K, Butler JN, Canepa A, Cerati GB, Cheung HWK, Chlebana F, Cremonesi M, Duarte J, Elvira VD, Freeman J, Gecse Z, Gottschalk E, Gray L, Green D, Grunendahl S, Gutsche O, Harris RM, Hasegawa S, Hirschauer J, Hu Z, Jayatilaka B, Jindariani S, Johnson M, Joshi U, Klima B, Kreis B, Lammel S, Lincoln D, Lipton R, Liu M, Liu T, De Sa RL, Lykken J, Maeshima K, Magini N, Marraffino JM, Maruyama S, Mason D, McBride P, Merkel P, Mrenna S, Nahn S, O'Dell V, Pedro K, Prokofyev O, Rakness G, Ristori L, Schneider B, Sexton-Kennedy E, Soha A, Spalding WJ, Spiegel L, Stoynev S, Strait J, Strobbe N, Taylor L, Tkaczyk S, Tran NV, Uplegger L, Vaandering EW, Vernieri C, Verzocchi M, Vidal R, Wang M, Weber HA, Whitbeck A, Acosta D, Avery P, Bortignon P, Bourilkov D, Brinkerhoff A, Carnes A, Carver M, Curry D, Das S, Field RD, Furic IK, Konigsberg J, Korytov A, Kotov K, Ma P, Matchev K, Mei H, Mitselmakher G, Rank D, Sperka D, Terentyev N, Thomas L, Wang J, Wang S, Yelton J, Joshi YR, Linn S, Markowitz P, Rodriguez JL, Ackert A, Adams T, Askew A, Hagopian S, Hagopian V, Johnson KF, Kolberg T, Martinez G, Perry T, Prosper H, Saha A, Santra A, Yohay R, Baarmand MM, Bhopatkar V, Colafranceschi S, Hohlmann M, Noonan D, Roy T, Yumiceva F, Adams MR, Apanasevich L, Berry D, Betts RR, Cavanaugh R, Chen X, Evdokimov O, Gerber CE, Hangal DA, Hofman DJ, Jung K, Kamin J, Gonzalez IDS, Tonjes MB, Trauger H, Varelas N, Wang H, Wu Z, Zhang J, Bilki B, Clarida W, Dilsiz K, Durgut S, Gandrajula RP, Haytmyradov M, Khristenko V, Merlo JP, Mermerkaya H, Mestvirishvili A, Moeller A, Nachtman J, Ogul H, Onel Y, Ozok F, Penzo A, Snyder C, Tiras E, Wetzel J, Yi K, Blumenfeld B, Cocoros A, Eminizer N, Fehling D, Feng L, Gritsan AV, Maksimovic P, Roskes J, Sarica U, Swartz M, Xiao M, You C, Al-bataineh A, Baringer P, Bean A, Boren S, Bowen J, Castle J, Khalil S, Kropivnitskaya A, Majumder D, Mcbrayer W, Murray M, Royon C, Sanders S, Schmitz E, Stringer R, Takaki JDT, Wang Q, Ivanov A, Kaadze K, Maravin Y, Mohammadi A, Saini LK, Skhirtladze N, Toda S, Rebassoo F, Wright D, Anelli C, Baden A, Baron O, Belloni A, Calvert B, Eno SC, Ferraioli C, Hadley NJ, Jabeen S, Jeng GY, Kellogg RG, Kunkle J, Mignerey AC, Ricci-Tam F, Shin YH, Skuja A, Tonwar SC, Abercrombie D, Allen B, Azzolini V, Barbieri R, Baty A, Bi R, Brandt S, Busza W, Cali IA, D'Alfonso M, Demiragli Z, Ceballos GG, Goncharov M, Hsu D, Iiyama Y, Innocenti GM, Klute M, Kovalskyi D, Lai YS, Lee YJ, Levin A, Luckey PD, Maier B, Marini AC, Mcginn C, Mironov C, Narayanan S, Niu X, Paus C, Roland C, Roland G, Salfeld-Nebgen J, Stephans GSF, Tatar K, Velicanu D, Wang J, Wang TW, Wyslouch B, Benvenuti AC, Chatterjee RM, Evans A, Hansen P, Kalafut S, Kubota Y, Lesko Z, Mans J, Nourbakhsh S, Ruckstuhl N, Rusack R, Turkewitz J, Acosta JG, Oliveros S, Avdeeva E, Bloom K, Claes DR, Fangmeier C, Suarez RG, Kamalieddin R, Kravchenko I, Monroy J, Siado JE, Snow GR, Stieger B, Alyari M, Dolen J, Godshalk A, Harrington C, Iashvili I, Nguyen D, Parker A, Rappoccio S, Roozbahani B, Alverson G, Barberis E, Hortiangtham A, Massironi A, Morse DM, Nash D, Orimoto T, De Lima RT, Trocino D, Wood D, Bhattacharya S, Charaf O, Hahn KA, Mucia N, Odell N, Pollack B, Schmitt MH, Sung K, Trovato M, Velasco M, Dev N, Hildreth M, Anampa KH, Jessop C, Karmgard DJ, Kellams N, Lannon K, Loukas N, Marinelli N, Meng F, Mueller C, Musienko Y, Planer M, Reinsvold A, Ruchti R, Smith G, Taroni S, Wayne M, Wolf M, Woodard A, Alimena J, Antonelli L, Bylsma B, Durkin LS, Flowers S, Francis B, Hart A, Hill C, Ji W, Liu B, Luo W, Puigh D, Winer BL, Wulsin HW, Benaglia A, Cooperstein S, Driga O, Elmer P, Hardenbrook J, Hebda P, Higginbotham S, Lange D, Luo J, Marlow D, Mei K, Ojalvo I, Olsen J, Palmer C, Piroue P, Stickland D, Tully C, Malik S, Norberg S, Barker A, Barnes VE, Folgueras S, Gutay L, Jha MK, Jones M, Jung AW, Khatiwada A, Miller DH, Neumeister N, Peng CC, Schulte JF, Sun J, Wang F, Xie W, Cheng T, Parashar N, Stupak J, Adair A, Akgun B, Chen Z, Ecklund KM, Geurts FJM, Guilbaud M, Li W, Michlin B, Northup M, Padley BP, Roberts J, Rorie J, Tu Z, Zabel J, Bodek A, de Barbaro P, Demina R, Duh YT, Ferbel T, Galanti M, Garcia-Bellido A, Han J, Hindrichs O, Khukhunaishvili A, Lo KH, Tan P, Verzetti M, Ciesielski R, Goulianos K, Mesropian C, Agapitos A, Chou JP, Gershtein Y, Espinosa TAG, Halkiadakis E, Heindl M, Hughes E, Kaplan S, Elayavalli RK, Kyriacou S, Lath A, Montalvo R, Nash K, Osherson M, Saka H, Salur S, Schnetzer S, Sheffield D, Somalwar S, Stone R, Thomas S, Thomassen P, Walker M, Delannoy AG, Foerster M, Heideman J, Riley G, Rose K, Spanier S, Thapa K, Bouhali O, Hernandez AC, Celik A, Dalchenko M, De Mattia M, Delgado A, Dildick S, Eusebi R, Gilmore J, Huang T, Kamon T, Mueller R, Pakhotin Y, Patel R, Perloff A, Perniee L, Rathjens D, Safonov A, Tatarinov A, Ulmer KA, Akchurin N, Damgov J, De Guio F, Dudero PR, Faulkner J, Gurpinar E, Kunori S, Lamichhane K, Lee SW, Libeiro T, Peltola T, Undleeb S, Volobouev I, Wang Z, Greene S, Gurrola A, Janjam R, Johns W, Maguire C, Melo A, Ni H, Sheldon P, Tuo S, Velkovska J, Xu Q, Arenton MW, Barria P, Cox B, Hirosky R, Ledovskoy A, Li H, Neu C, Sinthuprasith T, Sun X, Wang Y, Wolfe E, Xia F, Harr R, Karchin PE, Sturdy J, Zaleski S, Brodski M, Buchanan J, Caillol C, Dasu S, Dodd L, Duric S, Gomber B, Grothe M, Herndon M, Herve A, Hussain U, Klabbers P, Lanaro A, Levine A, Long K, Loveless R, Pierro GA, Polese G, Ruggles T, Savin A, Smith N, Smith WH, Taylor D, Woods N
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Search for electroweak production of charginos and neutralinos in WH events in proton-proton collisions at root s=13 TeV
JOURNAL OF HIGH ENERGY PHYSICS 2017 NOV 8; ?(11):? Article 029
Results are reported from a search for physics beyond the standard model in proton-proton collision events with a charged lepton (electron or muon), two jets identi fi ed as originating from a bottom quark decay, and signi fi cant imbalance in the transverse momentum. The search was performed using a data sample corresponding to 35.9 fb(-1), collected by the CMS experiment in 2016 at root s = 13 TeV. Events with this signature can arise, for example, from the electroweak production of gauginos, which are predicted in models based on supersymmetry. The event yields observed in data are consistent with the estimated standard model backgrounds. Limits are obtained on the cross sections for chargino-neutralino ((chi) over tilde (+/-)(1) (chi) over tilde (0)(2)) production in a simplified model of supersymmetry with the decays (chi) over tilde (+/-)(1) -> W-(chi) over tilde1(+/-)0 and (chi) over tilde (0)(2) -> H-(chi) over tilde1(0). Values of m((chi) over tilde1 +/-) between 220 and 490 GeV are excluded at 95% confidence level by this search when the (chi) over tilde (0)(1) is massless, and values of m((chi) over tilde 10) are excluded up to 110 GeV for m((chi) over tilde1 +/-) approximate to 450 GeV.
Gerwin PM, Arbona RJR, Riedel ER, Henderson KS, Lipman NS
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PCR Testing of IVC Filter Tops as a Method for Detecting Murine Pinworms and Fur Mites
JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE 2017 NOV; 56(6):752-761
We evaluated PCR testing of filter tops from cages maintained on an IVC system through which exhaust air is filtered at the cage level as a method for detecting parasite-infected and-infested cages. Cages containing 4 naive Swiss Webster mice received 360 mL of uncontaminated aspen chip or alpha-cellulose bedding (n = 18 cages each) and 60 mL of the same type of bedding weekly from each of the following 4 groups of cages housing mice infected or infested with Syphacia obvelata (SO), Aspiculuris tetraptera (AT), Myocoptes musculinus (MC), or Myobia musculi (MB) and Radfordia affinis (RA; 240 mL bedding total). Detection rates were compared at 30, 60, and 90 d after initiating bedding exposure, by using PCR analysis of filter tops (media extract and swabs) and testing of mouse samples (fur swab [direct] PCR testing, fecal flotation, anal tape test, direct examination of intestinal contents, and skin scrape). PCR testing of filter media extract detected 100% of all parasites at 30 d (both bedding types) except for AT (alpha-cellulose bedding, 67% detection rate); identified more cages with fur mites (MB and MC) than direct PCR when cellulose bedding was used; and was better at detecting parasites than all nonmolecular methods evaluated. PCR analysis of filter media extract was superior to swab and direct PCR for all parasites cumulatively for each bedding type. Direct PCR more effectively detected MC and all parasites combined for aspen chip compared with cellulose bedding. PCR analysis of filter media extract for IVC systems in which exhaust air is filtered at the cage level was shown to be a highly effective environmental testing method.
Yurieva O, Nikiforov V, Nikiforov V, O'Donnell M, Mustaev A
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Insights into RNA polymerase catalysis and adaptive evolution gained from mutational analysis of a locus conferring rifampicin resistance
NUCLEIC ACIDS RESEARCH 2017 NOV 2; 45(19):11327-11340
S531 of Escherichia coli RNA polymerase (RNAP) beta subunit is a part of RNA binding domain in transcription complex. While highly conserved, S531 is not involved in interactions within the transcription complex as suggested by X-ray analysis. To understand the basis for S531 conservation we performed systematic mutagenesis of this residue. We find that the most of the mutations significantly decreased initiation-to-elongation transition by RNAP. Surprisingly, some changes enhanced the production of full-size transcripts by suppressing abortive loss of short RNAs. S531-R increased transcript retention by establishing a salt bridge with RNA, thereby explaining the R substitution at the equivalent position in extremophilic organisms, in which short RNAs retention is likely to be an issue. Generally, the substitutions had the same effect on bacterial doubling time when measured at 20 degrees. Raising growth temperature to 37 degrees ablated the positive influence of some mutations on the growth rate in contrast to their in vitro action, reflecting secondary effects of cellular environment on transcription and complex involvement of 531 locus in the cell biology. The properties of generated RNAP variants revealed an RNA/protein interaction network that is crucial for transcription, thereby explaining the details of initiation-to-elongation transition on atomic level.
Cheal SM, Fung EK, Patel M, Xu H, Guo HF, Zanzonico PB, Monette S, Wittrup KD, Cheung NKV, Larson SM
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Curative Multicycle Radioimmunotherapy Monitored by Quantitative SPECT/CT-Based Theranostics, Using Bispecific Antibody Pretargeting Strategy in Colorectal Cancer
JOURNAL OF NUCLEAR MEDICINE 2017 NOV 1; 58(11):1735-1742
Radioimmunotherapy of solid tumors using antibody-targeted radionuclides has been limited by low therapeutic indices (TIs). We recently reported a novel 3-step pretargeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33 (GPA33)-targeting bispecific antibody and a small-molecule radioactive hapten, a complex of Lu-177 and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (Lu-177-DOTA-Bn), that leads to high TIs for radiosensitive tissues such as blood (TI = 73) and kidney (TI = 12). We tested our hypothesis that a fractionated anti-GPA33 DOTAPRIT regimen calibrated to deliver a radiation absorbed dose to tumor of more than 100 Gy would lead to a high probability of tumor cure while being well tolerated by nude mice bearing subcutaneous GPA33-positive SW1222 xenografts. Methods: We treated groups of nude mice bearing 7-d-old SW1222 xenografts with a fractionated 3-cycle anti-GPA33 DOTA-PRIT regimen (total administered Lu-177-DOTA-Bn activity, 167 MBq/mouse; estimated radiation absorbed dose to tumor, 110 Gy). In randomly selected mice undergoing treatment, serial SPECT/CT imaging was used to monitor treatment response and calculate radiation absorbed doses to tumor. Necropsy was done on surviving animals 100-200 d after treatment to determine frequency of cure and assess select normal tissues for treatment-related histopathologies. Results: Rapid exponential tumor progression was observed in control treatment groups (i.e., no treatment or 177Lu-DOTA-Bn only), leading to euthanasia due to excessive tumor burden, whereas 10 of 10 complete responses were observed for the DOTA-PRIT-treated animals within 30 d. Treatment was well tolerated, and 100% histologic cure was achieved in 9 of 9 assessable animals without detectable radiation damage to critical organs, including bone marrow and kidney. Radiation absorbed doses to tumor derived from SPECT/CT (102 Gy) and from biodistribution (110 Gy) agreed to within 6.9%. Of the total dose of approximately 100 Gy, the first dose contributes 30%, the second dose 60%, and the third dose 10%. Conclusion: In a GPA33-positive human colorectal cancer xenograft mouse model, we validated a SPECT/CT-based theranostic PRIT regimen that led to 100% complete responses and 100% cures without any treatmentrelated toxicities, based on high TIs for radiosensitive tissues. These studies support the view that anti-GPA33 DOTA-PRIT will be a potent radioimmunotherapy regimen for GPA33-positive colorectal cancer tumors in humans.
Wang J, Suarez-Farinas M, Estrada Y, Parker ML, Greenlees L, Stephens G, Krueger J, Guttman-Yassky E, Howell MD
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Identification of unique proteomic signatures in allergic and non-allergic skin disease
CLINICAL AND EXPERIMENTAL ALLERGY 2017 NOV; 47(11):1456-1467
Background: Atopic dermatitis (AD), psoriasis (PS), and contact dermatitis (CD) are common skin diseases, characterized by barrier disruption and systemic inflammation, with unique epidermal signatures and common inflammatory pathways identified by transcriptomic profiling. This study profiled proteomic signatures in serum from subjects with AD, PS, and CD compared with healthy controls (HC). Objective: Identify unique proteomic signatures to distinguish between inflammatory diseases with similar epidermal disruption and overlapping epithelial inflammation. Methods: Sera from 20 subjects with moderate to severe AD, 10 subjects with CD, 12 subjects with moderate to severe PS, 10 subjects with both AD and CD, and 10 HC with no history of skin disease was analysed using high-throughput proteomic analysis that detects expression of 1129 protein targets. Protein expression was compared between disease and HC, and across diseases for statistical significance (fold change >= 1.5 and false discovery rate <= 0.05), to identify unique proteomic signatures for each disease. Results: Complement C5A anaphylatoxin (C5A), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), ILT-4, C-C motif ligand 18 (PARC), and sialic acidbinding Ig-like lectin 14 (SIG14) were significantly modulated in all three diseases compared with HC. We identified unique signatures for AD (Immunoglobulin E (IgE), thymus-and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC)), CD (10 proteins), and PS (kynureninase (KYNU)). Proteomic profiling in subjects with both AD and CD identified additional dysregulated proteins compared with subjects with either condition alone, indicating an exacerbated inflammation reaction. Conclusions and Clinical Relevance: Unique sera proteomic signatures may distinguish between inflammatory skin diseases despite similar epidermal barrier disruption and epithelial inflammation. This may provide insight into disease pathogenesis, diagnosis, and therapeutic intervention in difficult-to-treat subjects.
Alvarez SW, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL, Adams S, Sabatini DM, Birsoy K, Possemato R
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NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis
NATURE 2017 NOV 30; 551(7682):639-643
Environmental nutrient levels impact cancer cell metabolism, resulting in context-dependent gene essentiality(1,2). Here, using loss-of-function screening based on RNA interference, we show that environmental oxygen levels are a major driver of differential essentiality between in vitro model systems and in vivo tumours. Above the 3-8% oxygen concentration typical of most tissues, we find that cancer cells depend on high levels of the iron-sulfur cluster biosynthetic enzyme NFS1. Mammary or subcutaneous tumours grow despite suppression of NFS1, whereas metastatic or primary lung tumours do not. Consistent with a role in surviving the high oxygen environment of incipient lung tumours, NFS1 lies in a region of genomic amplification present in lung adenocarcinoma and is most highly expressed in well-differentiated adenocarcinomas. NFS1 activity is particularly important for maintaining the ironsulfur co-factors present in multiple cell-essential proteins upon exposure to oxygen compared to other forms of oxidative damage. Furthermore, insufficient iron-sulfur cluster maintenance robustly activates the iron-starvation response and, in combination with inhibition of glutathione biosynthesis, triggers ferroptosis, a non-apoptotic form of cell death. Suppression of NFS1 cooperates with inhibition of cysteine transport to trigger ferroptosis in vitro and slow tumour growth. Therefore, lung adenocarcinomas select for expression of a pathway that confers resistance to high oxygen tension and protects cells from undergoing ferroptosis in response to oxidative damage.
Conceicao T, de Lencastre H, Aires-De-Sousa M
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Carriage of Staphylococcus aureus among Portuguese nursing students: A longitudinal cohort study over four years of education
PLOS ONE 2017 NOV 30; 12(11):? Article e0188855
Background Staphylococcus aureus is a major human pathogen that can colonize healthy people mainly in the anterior nares. The aim of the present study was to evaluate S. aureus nasal colonization over time among Portuguese nursing students, including methicillin-resistant S. aureus (MRSA). Methods and findings In this longitudinal cohort study, we collected 280 nasal swabs from nursing students at 14 time points over four years of schooling (2012-2016). The isolates were characterized by pulsed-field gel electrophoresis (PFGE), spa typing, multilocus sequence typing (MLST), and SCCmec typing for MRSA. Among 47 students, 20 (43%) carried methicillin-susceptible S. aureus (MSSA) at admission, but none was colonized with MRSA. A total of 19 students (40%) became colonized after exposure during the nursing training, out of which five carried MRSA. Overall, 39 students (83%) had S. aureus detected at least once during the study period. Among the 97 MSSA isolates, most (65%) belonged to four clones: PFGE A-ST30 (21%), B-ST72 (20%), C-ST508 (13%), and D-ST398 (11%). Three of the five MRSA carriers were colonized with the predominant clone circulating in Portuguese hospitals (ST22-IVh) and two with ST3162-II. Colonization of nursing students was highly dynamic with continuous appearance of strains with distinct PFGE types in the same individual. Conclusions A considerable proportion of students became colonized by S. aureus, including MRSA, during the nursing education, evidencing this population represents an important reservoir of S. aureus. Therefore, education on infection control measures in nursing schools is of major importance.