@article{brown_chen_ivanova_leekitcharoenphon_parsons_niedermeyer_gould_strules_mesa-cruz_kelly_et al._2023, title={Draft Genome Sequences of 158 Listeria monocytogenes Strains Isolated from Black Bears (Ursus americanus) in the United States}, volume={12}, ISSN={2576-098X}, url={http://dx.doi.org/10.1128/mra.00248-23}, DOI={10.1128/mra.00248-23}, abstractNote={Listeria monocytogenes is responsible for severe foodborne disease and major economic losses, but its potential reservoirs in natural ecosystems remain poorly understood. Here, we report the draft genome sequences of 158 L. monocytogenes strains isolated from black bears (Ursus americanus) in the southeastern United States between 2014 and 2017. ABSTRACT Listeria monocytogenes is responsible for severe foodborne disease and major economic losses, but its potential reservoirs in natural ecosystems remain poorly understood. Here, we report the draft genome sequences of 158 L. monocytogenes strains isolated from black bears (Ursus americanus) in the southeastern United States between 2014 and 2017.}, number={7}, journal={Microbiology Resource Announcements}, publisher={American Society for Microbiology}, author={Brown, Phillip and Chen, Yi and Ivanova, Mirena and Leekitcharoenphon, Pimlapas and Parsons, Cameron and Niedermeyer, Jeffrey and Gould, Nicholas and Strules, Jennifer and Mesa-Cruz, J. Bernardo and Kelly, Marcella J. and et al.}, editor={Rasko, DavidEditor}, year={2023}, month={Jul} } @article{brown_kanenaka_chen_ivanova_leekitcharoenphon_elhanafi_kathariou_2023, title={Draft Genome Sequences of Closely Related Listeria monocytogenes Lineage III Strains Isolated from a Food Processing Environment and a Case of Human Listeriosis}, volume={5}, ISSN={["2576-098X"]}, url={https://doi.org/10.1128/mra.00250-23}, DOI={10.1128/mra.00250-23}, abstractNote={Listeria monocytogenes lineage III is genetically highly diverse, and closely related lineage III strains from food facilities and human listeriosis have not been reported. Here, we report the genome sequences of three closely related lineage III strains from Hawaii, namely, one isolated from a human case and two isolated from a produce storage facility. ABSTRACT Listeria monocytogenes lineage III is genetically highly diverse, and closely related lineage III strains from food facilities and human listeriosis have not been reported. Here, we report the genome sequences of three closely related lineage III strains from Hawaii, namely, one isolated from a human case and two isolated from a produce storage facility.}, journal={MICROBIOLOGY RESOURCE ANNOUNCEMENTS}, author={Brown, Phillip and Kanenaka, Rebecca and Chen, Yi and Ivanova, Mirena and Leekitcharoenphon, Pimlapas and Elhanafi, Driss and Kathariou, Sophia}, editor={Rasko, DavidEditor}, year={2023}, month={May} } @article{lee_tham_danielsson-tham_lopez-valladares_chen_brown_kathariou_2023, title={Draft Genome Sequences of Heavy Metal-Resistant Listeria monocytogenes Strains of Sequence Type 14 (Clonal Complex 14) from Human Listeriosis Cases in Sweden}, volume={7}, ISSN={["2576-098X"]}, url={https://doi.org/10.1128/mra.00406-23}, DOI={10.1128/mra.00406-23}, abstractNote={Listeria monocytogenes of clonal complex 14 (CC14) is a potentially hypervirulent clone of serotype 1/2a but remains poorly characterized. We report the genome sequences of five sequence type 14 (ST14) (CC14) strains from human listeriosis cases in Sweden, which harbor a chromosomal heavy metal resistance island that is generally uncommon in serotype 1/2a. ABSTRACT Listeria monocytogenes of clonal complex 14 (CC14) is a potentially hypervirulent clone of serotype 1/2a but remains poorly characterized. We report the genome sequences of five sequence type 14 (ST14) (CC14) strains from human listeriosis cases in Sweden, which harbor a chromosomal heavy metal resistance island that is generally uncommon in serotype 1/2a.}, journal={MICROBIOLOGY RESOURCE ANNOUNCEMENTS}, author={Lee, Sangmi and Tham, Wilhelm and Danielsson-Tham, Marie-Louise and Lopez-Valladares, Gloria and Chen, Yi and Brown, Phillip and Kathariou, Sophia}, editor={Dennehy, John J.Editor}, year={2023}, month={Jul} } @article{brown_murray_galsworthy_ivanova_leekitcharoenphon_ward_kucerova_chen_elhanafi_siletzky_et al._2023, title={Draft genome sequences of a historical collection of Listeria monocytogenes from humans and other sources, 1926-1964}, volume={9}, ISSN={["2576-098X"]}, url={https://doi.org/10.1128/MRA.00625-23}, DOI={10.1128/MRA.00625-23}, abstractNote={ABSTRACT Listeria monocytogenes can persistently contaminate food processing environments and tolerate sanitizers. Most sequenced strains are from clinical and environmental sources in the contemporary era, with relatively few prior to extensive food processing and sanitizer use. We report the genome sequences of a diverse panel of 83 strains from 1926 to 1964.}, journal={MICROBIOLOGY RESOURCE ANNOUNCEMENTS}, author={Brown, Phillip and Murray, Robert G. E. and Galsworthy, Sara and Ivanova, Mirena and Leekitcharoenphon, Pimlapas and Ward, Todd and Kucerova, Zuzana and Chen, Yi and Elhanafi, Driss and Siletzky, Robin and et al.}, editor={Dennehy, John J.Editor}, year={2023}, month={Sep} } @article{brown_lee_elhanafi_tham_danielsson-tham_lopez-valladares_chen_ivanova_leekitcharoenphon_kathariou_2023, title={Investigation of a Listeria monocytogenes Chromosomal Immigration Control Region Reveals Diverse Restriction Modification Systems with Complete Sequence Type Conservation}, volume={11}, ISSN={["2076-2607"]}, url={https://doi.org/10.3390/microorganisms11030699}, DOI={10.3390/microorganisms11030699}, abstractNote={Listeria monocytogenes is a Gram-positive pathogen responsible for the severe foodborne disease listeriosis. A chromosomal hotspot between lmo0301 and lmo0305 has been noted to harbor diverse restriction modification (RM) systems. Here, we analyzed 872 L. monocytogenes genomes to better understand the prevalence and types of RM systems in this region, designated the immigration control region (ICR). Type I, II, III and IV RM systems were found in 86.1% of strains inside the ICR and in 22.5% of strains flanking the ICR. ICR content was completely conserved within the same multilocus sequence typing-based sequence type (ST), but the same RM system could be identified in diverse STs. The intra-ST conservation of ICR content suggests that this region may drive the emergence of new STs and promote clone stability. Sau3AI-like, LmoJ2 and LmoJ3 type II RM systems as well as type I EcoKI-like, and type IV AspBHI-like and mcrB-like systems accounted for all RM systems in the ICR. A Sau3AI-like type II RM system with specificity for GATC was harbored in the ICR of many STs, including all strains of the ancient, ubiquitous ST1. The extreme paucity of GATC recognition sites in lytic phages may reflect ancient adaptation of these phages to preempt resistance associated with the widely distributed Sau3AI-like systems. These findings indicate that the ICR has a high propensity for RM systems which are intraclonaly conserved and may impact bacteriophage susceptibility as well as ST emergence and stability.}, number={3}, journal={MICROORGANISMS}, author={Brown, Phillip and Lee, Sangmi and Elhanafi, Driss and Tham, Wilhelm and Danielsson-Tham, Marie-Louise and Lopez-Valladares, Gloria and Chen, Yi and Ivanova, Mirena and Leekitcharoenphon, Pimlapas and Kathariou, Sophia}, year={2023}, month={Mar} } @article{brown_hernandez_parsons_chen_gould_deperno_niedermeyer_kathariou_2023, title={Tetracycline resistance in Listeria monocytogenes and L. innocua from wild black bears (Ursus americanus) in the United States is mediated by novel transposable elements}, volume={89}, ISSN={["1098-5336"]}, url={https://doi.org/10.1128/aem.01205-23}, DOI={10.1128/aem.01205-23}, abstractNote={ABSTRACT Listeria monocytogenes is a facultative intracellular foodborne pathogen and the causative agent of the severe disease listeriosis. It is found ubiquitously in the environment and exhibits innate resistance to certain antimicrobials, but acquired antimicrobial resistance remains relatively uncommon. Given the potentially dire health outcomes associated with listeriosis, acquisition of antimicrobial resistance (AMR) by this pathogen is of considerable public health concern. AMR in L. monocytogenes has been surveyed frequently in strains of clinical and food origin, but much less commonly in wildlife. We analyzed 158 strains of L. monocytogenes and 27 of non-pathogenic Listeria spp. isolated from wild black bears (Ursus americanus) for resistance to a panel of antimicrobials. AMR was uncommon and noted mostly for tetracycline. Tetracycline resistance was more common in Listeria innocua than in L. monocytogenes. All tetracycline-resistant L. monocytogenes strains belonged to sequence type ST1039 and harbored the Tn916-like tet(M) transposon Tn916.1039 in a conserved chromosomal location. In contrast, three different tetracycline resistance elements, i.e., the tet(M) elements Tn5801.UAM and Tn5801.551 and the tet(S) element Tn6000.205, were identified among tetracycline-resistant strains of L. innocua. The greater prevalence and diversity of tetracycline resistance elements among bear-derived non-pathogenic Listeria strains suggest the potential of the latter to serve as reservoirs for retention and diversification of AMR determinants in this wildlife host and warrant their further monitoring and study. IMPORTANCE Listeria monocytogenes causes severe foodborne illness and is the only human pathogen in the genus Listeria. Previous surveys of AMR in Listeria focused on clinical sources and food or food processing environments, with AMR in strains from wildlife and other natural ecosystems remaining under-explored. We analyzed 185 sequenced strains from wild black bears (Ursus americanus) from the United States, including 158 and 27 L. monocytogenes and L. innocua, respectively. Tetracycline resistance was the most prevalent resistance trait. In L. monocytogenes, it was encountered exclusively in serotype 4b strains with the novel Tn916-like element Tn916.1039. In contrast, three distinct, novel tetracycline resistance elements (Tn5801.UAM, Tn5801.551, and Tn6000.205) were identified in L. innocua. Interestingly, Tn5801.551 was identical to elements in L. monocytogenes from a major foodborne outbreak in the United States in 2011. The findings suggest the importance of wildlife and non-pathogenic Listeria species as reservoir for resistance elements in Listeria. Listeria monocytogenes causes severe foodborne illness and is the only human pathogen in the genus Listeria. Previous surveys of AMR in Listeria focused on clinical sources and food or food processing environments, with AMR in strains from wildlife and other natural ecosystems remaining under-explored. We analyzed 185 sequenced strains from wild black bears (Ursus americanus) from the United States, including 158 and 27 L. monocytogenes and L. innocua, respectively. Tetracycline resistance was the most prevalent resistance trait. In L. monocytogenes, it was encountered exclusively in serotype 4b strains with the novel Tn916-like element Tn916.1039. In contrast, three distinct, novel tetracycline resistance elements (Tn5801.UAM, Tn5801.551, and Tn6000.205) were identified in L. innocua. Interestingly, Tn5801.551 was identical to elements in L. monocytogenes from a major foodborne outbreak in the United States in 2011. The findings suggest the importance of wildlife and non-pathogenic Listeria species as reservoir for resistance elements in Listeria.}, number={11}, journal={Environmental Microbiology}, author={Brown, Phillip and Hernandez, Kevin and Parsons, Cameron and Chen, Yi and Gould, Nicholas and DePerno, Christopher S. and Niedermeyer, Jeffrey and Kathariou, Sophia}, editor={Dozois, Charles M.Editor}, year={2023}, month={Nov} } @article{brown_kucerova_gorski_chen_ivanova_leekitcharoenphon_parsons_niedermeyer_jackson_kathariou_2022, title={Horizontal Gene Transfer and Loss of Serotype-Specific Genes in Listeria monocytogenes Can Lead to Incorrect Serotype Designations with a Commonly-Employed Molecular Serotyping Scheme}, volume={12}, ISSN={["2165-0497"]}, url={https://doi.org/10.1128/spectrum.02745-22}, DOI={10.1128/spectrum.02745-22}, abstractNote={Listeria monocytogenes is a foodborne pathogen responsible for severe illness (listeriosis), especially in pregnant women and their fetuses, immunocompromised individuals, and the elderly. Three serotypes, 1/2a, 1/2b, and 4b, account for most human listeriosis, with certain serotype 4b clonal complexes (CCs) overrepresented in human disease. ABSTRACT Listeria monocytogenes is a Gram-positive, facultative intracellular foodborne pathogen capable of causing severe, invasive illness (listeriosis). Three serotypes, 1/2a, 1/2b, and 4b, are leading contributors to human listeriosis, with 4b including the major hypervirulent clones. The multiplex PCR scheme developed by Doumith and collaborators employs primers targeting specific lineages (e.g., lineage II-specific lmo0737, lineage I-specific LMOf2365_2059) or serotypes (e.g., serotype 4b-specific LMOf2365_1900). The Doumith scheme (DS) is extensively employed for molecular serotyping of L. monocytogenes due to its high accuracy, relative ease, and affordability. However, for certain strains, the DS serotype designations are in conflict with those relying on antibody-based schemes or whole-genome sequence (WGS) analysis. In the current study, all 27 tested serotype 4b strains with sequence type 782 (ST782) within the hypervirulent clonal complex 2 (CC2) were designated 1/2b/3b using the DS. These strains lacked the serotype 4b-specific gene LMOf2365_1900, while retaining LMOf2365_2059, which, together with prs, yields the DS 1/2b/3b profile. Furthermore, 15 serotype 1/2a strains of four STs, mostly from water, were designated 1/2b/3b using the DS. These strains lacked the lmo0737 cassette but harbored genomic islands with LMOf2365_2059, thus yielding the DS 1/2b/3b profile. Lastly, we investigated a novel, dual 1/2a-1/2b profile obtained using the DS with 21 serotype 1/2a strains of four STs harboring both the lmo0737 cassette and genomic islands with LMOf2365_2059. The findings suggest that for certain strains and clones of L. monocytogenes the DS designations should be viewed with caution and complemented with alternative tools, e.g., traditional serotyping or WGS analysis. IMPORTANCE Listeria monocytogenes is a foodborne pathogen responsible for severe illness (listeriosis), especially in pregnant women and their fetuses, immunocompromised individuals, and the elderly. Three serotypes, 1/2a, 1/2b, and 4b, account for most human listeriosis, with certain serotype 4b clonal complexes (CCs) overrepresented in human disease. Serotyping remains extensively employed in Listeria epidemiologic investigations, and a multiplex PCR-based serotyping scheme is widely used. However, the PCR gene targets can be lost or gained via horizontal gene transfer, leading to novel PCR profiles without known serotype designations or to incorrect serotype assignments. Thus, an entire serotype 4b clone of the hypervirulent CC2 would be misidentified as serotype 1/2b, and several strains of serotype 1/2a would be identified as serotype 1/2b. Such challenges are especially common in novel clones from underexplored habitats, e.g., wildlife and surface water. The findings suggest caution in application of molecular serotyping, while highlighting Listeria’s diversity and potential for horizontal gene transfer.}, journal={MICROBIOLOGY SPECTRUM}, author={Brown, Phillip and Kucerova, Zuzana and Gorski, Lisa and Chen, Yi and Ivanova, Mirena and Leekitcharoenphon, Pimlapas and Parsons, Cameron and Niedermeyer, Jeffrey and Jackson, James and Kathariou, Sophia}, editor={Chousalkar, KapilEditor}, year={2022}, month={Dec} } @article{brown_chen_siletzky_parsons_jaykus_eifert_ryser_logue_stam_brown_et al._2021, title={Harnessing Whole Genome Sequence Data for Facility-Specific Signatures for Listeria monocytogenes: A Case Study With Turkey Processing Plants in the United States}, volume={5}, ISSN={["2571-581X"]}, url={http://dx.doi.org/10.3389/fsufs.2021.742353}, DOI={10.3389/fsufs.2021.742353}, abstractNote={Listeria monocytogenes is a Gram-positive foodborne pathogen responsible for the severe disease listeriosis and notorious for its ability to persist in food processing plants, leading to contamination of processed, ready-to-eat foods. L. monocytogenes persistence in various food processing environments (FPEs) has been extensively investigated by various subtyping tools, with increasing use of whole genome sequencing (WGS). However, major knowledge gaps remain. There is a need for facility-specific molecular signatures not only for adequate attribution of L. monocytogenes to a specific FPE but also for improved understanding of the ecology and evolution of L. monocytogenes in the food processing ecosystem. Furthermore, multiple strains can be recovered from a single FPE sample, but their diversity can be underestimated with common molecular subtyping tools. In this study we investigated a panel of 54 L. monocytogenes strains from four turkey processing plants in the United States. A combination of WGS and phenotypic assays was employed to assess strain persistence as well as identify facility-specific molecular signatures. Comparative analysis of allelic variation across the whole genome revealed that allelic profiles have the potential to be specific to individual processing plants. Certain allelic profiles remained associated with individual plants even when closely-related strains from other sources were included in the analysis. Furthermore, for certain sequence types (STs) based on the seven-locus multilocus sequence typing scheme, presence and location of premature stop codons in inlA, inlB length, prophage sequences, and the sequence content of a genomic hotspot could serve as plant-specific signatures. Interestingly, the analysis of different isolates from the same environmental sample revealed major differences not only in serotype and ST, but even in the sequence content of strains of the same ST. This study highlights the potential for WGS data to be deployed for identification of facility-specific signatures, thus facilitating the tracking of strain movement through the food chain. Furthermore, deployment of WGS for intra-sample strain analysis allows for a more complete environmental surveillance of L. monocytogenes in food processing facilities, reducing the risk of failing to detect strains that may be clinically relevant and potentially novel.}, journal={FRONTIERS IN SUSTAINABLE FOOD SYSTEMS}, publisher={Frontiers Media SA}, author={Brown, Phillip and Chen, Yi and Siletzky, Robin and Parsons, Cameron and Jaykus, Lee-Ann and Eifert, Joseph and Ryser, Elliot and Logue, Catherine M. and Stam, Christina and Brown, Eric and et al.}, editor={Brown, PhillipEditor}, year={2021}, month={Oct} } @misc{parsons_brown_kathariou_2021, title={Use of Bacteriophage Amended with CRISPR-Cas Systems to Combat Antimicrobial Resistance in the Bacterial Foodborne Pathogen Listeria monocytogenes}, volume={10}, ISSN={["2079-6382"]}, url={http://dx.doi.org/10.3390/antibiotics10030308}, DOI={10.3390/antibiotics10030308}, abstractNote={Listeria monocytogenes is a bacterial foodborne pathogen and the causative agent of the disease listeriosis, which though uncommon can result in severe symptoms such as meningitis, septicemia, stillbirths, and abortions and has a high case fatality rate. This pathogen can infect humans and other animals, resulting in massive health and economic impacts in the United States and globally. Listeriosis is treated with antimicrobials, typically a combination of a beta-lactam and an aminoglycoside, and L. monocytogenes has remained largely susceptible to the drugs of choice. However, there are several reports of antimicrobial resistance (AMR) in both L. monocytogenes and other Listeria species. Given the dire health outcomes associated with listeriosis, the prospect of antimicrobial-resistant L. monocytogenes is highly problematic for human and animal health. Developing effective tools for the control and elimination of L. monocytogenes, including strains with antimicrobial resistance, is of the utmost importance to prevent further dissemination of AMR in this pathogen. One tool that has shown great promise in combating antibiotic-resistant pathogens is the use of bacteriophages (phages), which are natural bacterial predators and horizontal gene transfer agents. Although native phages can be effective at killing antibiotic-resistant pathogens, limited host ranges and evolved resistance to phages can compromise their use in the efforts to mitigate the global AMR challenge. However, recent advances can allow the use of CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) to selectively target pathogens and their AMR determinants. Employment of CRISPR-Cas systems for phage amendment can overcome previous limitations in using phages as biocontrol and allow for the effective control of L. monocytogenes and its AMR determinants.}, number={3}, journal={ANTIBIOTICS-BASEL}, publisher={MDPI AG}, author={Parsons, Cameron and Brown, Phillip and Kathariou, Sophia}, editor={Brown, PhillipEditor}, year={2021}, month={Mar} } @article{brown_chen_parsons_brown_loessner_shen_kathariou_2021, title={Whole Genome Sequence Analysis of Phage-Resistant Listeria monocytogenes Serotype 1/2a Strains from Turkey Processing Plants}, volume={10}, ISSN={["2076-0817"]}, url={http://dx.doi.org/10.3390/pathogens10020199}, DOI={10.3390/pathogens10020199}, abstractNote={Listeria monocytogenes is a Gram-positive bacterial pathogen and the causative agent of listeriosis, a severe foodborne infection. L. monocytogenes is notorious for its ability to persist in food processing environments (FPEs) via a variety of adaptive traits. Even though traits such as cold tolerance, biofilm formation and sanitizer resistance have been extensively investigated for their roles in persistence of L. monocytogenes in FPEs, much less is known about resistance to bacteriophages. Previous studies explored phage resistance mechanisms in laboratory-created mutants but it is imperative to investigate phage resistance that is naturally exhibited in FPE-derived strains. Here, we integrated the analysis of whole genome sequence data from a panel of serotype 1/2a strains of sequence types 321 and 391 from turkey processing plants, with the determination of cell surface substituents required for phage adsorption and phage infection assays with the four wide-host-range phages A511, P100, 20422-1 and 805405-1. Using a specific set of recombinant phage protein probes, we discovered that phage-resistant strains lacked one or both of the serogroup 1/2-specific wall teichoic acid carbohydrate decorations, N-acetylglucosamine and rhamnose. Furthermore, these phage-resistant strains harbored substitutions in lmo1080, lmo1081, and lmo2550, which mediate carbohydrate decoration of the wall teichoic acids.}, number={2}, journal={PATHOGENS}, publisher={MDPI AG}, author={Brown, Phillip and Chen, Yi and Parsons, Cameron and Brown, Eric and Loessner, Martin J. and Shen, Yang and Kathariou, Sophia}, editor={Brown, PhillipEditor}, year={2021}, month={Feb} } @article{parsons_niedermeyer_gould_brown_strules_parsons_bernardo mesa‐cruz_kelly_hooker_chamberlain_et al._2020, title={Listeria monocytogenes at the human–wildlife interface: black bears ( Ursus americanus ) as potential vehicles for Listeria}, volume={13}, ISBN={1751-7915}, ISSN={1751-7915 1751-7915}, url={http://dx.doi.org/10.1111/1751-7915.13509}, DOI={10.1111/1751-7915.13509}, abstractNote={Listeria monocytogenes is the causative agent of the foodborne illness listeriosis, which can result in severe symptoms and death in susceptible humans and other animals. L. monocytogenes is ubiquitous in the environment and isolates from food and food processing, and clinical sources have been extensively characterized. However, limited information is available on L. monocytogenes from wildlife, especially from urban or suburban settings. As urban and suburban areas are expanding worldwide, humans are increasingly encroaching into wildlife habitats, enhancing the frequency of human–wildlife contacts and associated pathogen transfer events. We investigated the prevalence and characteristics of L. monocytogenes in 231 wild black bear capture events between 2014 and 2017 in urban and suburban sites in North Carolina, Georgia, Virginia and United States, with samples derived from 183 different bears. Of the 231 captures, 105 (45%) yielded L. monocytogenes either alone or together with other Listeria. Analysis of 501 samples, primarily faeces, rectal and nasal swabs for Listeria spp., yielded 777 isolates, of which 537 (70%) were L. monocytogenes. Most L. monocytogenes isolates exhibited serotypes commonly associated with human disease: serotype 1/2a or 3a (57%), followed by the serotype 4b complex (33%). Interestingly, approximately 50% of the serotype 4b isolates had the IVb‐v1 profile, associated with emerging clones of L. monocytogenes. Thus, black bears may serve as novel vehicles for L. monocytogenes, including potentially emerging clones. Our results have significant public health implications as they suggest that the ursine host may preferentially select for L. monocytogenes of clinically relevant lineages over the diverse listerial populations in the environment. These findings also help to elucidate the ecology of L. monocytogenes and highlight the public health significance of the human–wildlife interface.}, number={3}, journal={Microbial Biotechnology}, publisher={Wiley}, author={Parsons, Cameron and Niedermeyer, Jeff and Gould, Nicholas and Brown, Phillip and Strules, Jennifer and Parsons, Arielle W. and Bernardo Mesa‐Cruz, J. and Kelly, Marcella J. and Hooker, Michael J. and Chamberlain, Michael J. and et al.}, editor={Brown, PhillipEditor}, year={2020}, month={May}, pages={706–721} } @article{parsons_costolo_brown_kathariou_2017, title={Penicillin-binding protein encoded by pbp4 is involved in mediating copper stress in Listeria monocytogenes}, volume={364}, ISSN={["1574-6968"]}, url={http://dx.doi.org/10.1093/femsle/fnx207}, DOI={10.1093/femsle/fnx207}, abstractNote={ABSTRACT Listeria monocytogenes raises major food safety and public health concerns due to its potential for severe foodborne disease and persistent colonization of food processing facilities. Copper is often employed to control pathogens in agriculture and is increasingly used in healthcare facilities, but mechanisms mediating tolerance of L. monocytogenes to copper remain poorly understood. A mariner‐based mutant library of L. monocytogenes 2011L‐2858, implicated in the 2011 listeriosis outbreak via whole cantaloupe, was screened for growth at sublethal levels of copper yielding mutant G2B4 with decreased copper tolerance. The transposon was localized in pbp4 (lmo2229 homolog), encoding a penicillin‐binding protein (PBP). In addition to reduced copper tolerance, G2B4 exhibited increased susceptibility to &bgr;‐lactam antibiotics, reduced biofilm formation and reduced virulence in the Galleria mellonella model. Mutant phenotypes were fully restored upon genetic complementation of G2B4 with intact pbp4. Findings provide the first evidence for the role of a PBP in copper tolerance of L. monocytogenes and suggest that pbp4 may be a suitable target to enable the use of lower levels of copper or enhance the effectiveness of levels currently in use. Given the wide distribution of PBPs and their highly conserved nature, this could have profound impacts in regard to ecology and control of L. monocytogenes and other microorganisms.}, number={20}, journal={FEMS MICROBIOLOGY LETTERS}, publisher={Oxford University Press (OUP)}, author={Parsons, Cameron and Costolo, Ben and Brown, Phillip and Kathariou, Sophia}, editor={Brown, PhillipEditor}, year={2017}, month={Oct} }