{"doi":"10.1128/aem.01475-25","title":"Stringent response-mediated ferroptosis-like death resistance underlies\n                    <i>Novosphingobium</i>\n                    persistence during ciprofloxacin stress","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title/>\n                    <jats:p>\n                      Antibiotics, as emerging hazardous materials in the environment, pose significant risks to ecosystems and contribute to the spread of antibiotic-resistant bacteria. Although extensive knowledge has been accumulated on antibiotic-resistance mechanisms in individual bacteria, less is understood about how the bacterial communities respond to antibiotic exposure under natural environmental conditions, where nutrient supplies are often limited and fluctuating. Here, we report that\n                      <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                      dominated in a wetland bacterial community under 1 µg/mL ciprofloxacin (CIP) exposure and persisted during DL-serine hydroxamate-induced starvation, where the stringent response alarmer (p)ppGpp was detected. Metagenome sequencing revealed that genes associated with siderophore transport, cytochrome\n                      <jats:italic toggle=\"yes\">c</jats:italic>\n                      , and glutathione S-transferase were significantly enriched in\n                      <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                      , linking its dominance under CIP stress to iron homeostasis and oxidative stress responses. Further study on the survival mechanism of\n                      <jats:italic toggle=\"yes\">Novosphingobium pentaromativorans</jats:italic>\n                      US6-1 under 8 µg/mL CIP stress demonstrated that stringent response regulated the growth rate and maintained cell viability by suppressing the TCA cycle and oxidative phosphorylation, deterring the entry of CIP and siderophore into cells, reducing intracellular ferrous iron and malondialdehyde, and balancing cellular redox status, thereby protecting cells from ferroptosis-like death. This study is the first to report\n                      <jats:italic toggle=\"yes\">Novosphingobium’s</jats:italic>\n                      dominance and persistence in a bacterial community during CIP stress in natural environmental conditions and to propose the stringent response-mediated ferroptosis-like death resistance as one of its key survival mechanisms.\n                    </jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE</jats:title>\n                      <jats:p>\n                        Antibiotics in the environment are increasingly recognized as a new class of pollutants that accelerate the evolutionary selection of antibiotic-resistant bacteria. However, little is known about how this selection occurs under natural conditions, including how specific bacteria taxa and mechanisms respond to particular antibiotics. This study reveals for the first time the selection effect of CIP on\n                        <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                        under nutrient-limited conditions, during which stringent response and iron homeostasis play important roles. An innovative linkage between stringent response and ferroptosis-like death resistance is proposed in\n                        <jats:italic toggle=\"yes\">N. pentaromativorans</jats:italic>\n                        US6-1, which serves as the CIP resistance mechanism for\n                        <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                        . These findings may help inform strategies to combat antimicrobial resistance in the natural environment.\n                      </jats:p>\n                    </jats:sec>\n                  </jats:sec>","journal":"Applied and Environmental Microbiology","year":2025,"id":668965,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1747038,"name":"Yili Huang","orcid":"0000-0003-4703-7954","position":1,"is_corresponding":false},{"id":441269,"name":"Qian Xu","orcid":"0000-0001-9521-7912","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Stringent response-mediated ferroptosis-like death resistance underlies\n                    <i>Novosphingobium</i>\n                    persistence during ciprofloxacin stress","abstract":"<jats:title>ABSTRACT</jats:title>\n                  <jats:sec>\n                    <jats:title/>\n                    <jats:p>\n                      Antibiotics, as emerging hazardous materials in the environment, pose significant risks to ecosystems and contribute to the spread of antibiotic-resistant bacteria. Although extensive knowledge has been accumulated on antibiotic-resistance mechanisms in individual bacteria, less is understood about how the bacterial communities respond to antibiotic exposure under natural environmental conditions, where nutrient supplies are often limited and fluctuating. Here, we report that\n                      <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                      dominated in a wetland bacterial community under 1 µg/mL ciprofloxacin (CIP) exposure and persisted during DL-serine hydroxamate-induced starvation, where the stringent response alarmer (p)ppGpp was detected. Metagenome sequencing revealed that genes associated with siderophore transport, cytochrome\n                      <jats:italic toggle=\"yes\">c</jats:italic>\n                      , and glutathione S-transferase were significantly enriched in\n                      <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                      , linking its dominance under CIP stress to iron homeostasis and oxidative stress responses. Further study on the survival mechanism of\n                      <jats:italic toggle=\"yes\">Novosphingobium pentaromativorans</jats:italic>\n                      US6-1 under 8 µg/mL CIP stress demonstrated that stringent response regulated the growth rate and maintained cell viability by suppressing the TCA cycle and oxidative phosphorylation, deterring the entry of CIP and siderophore into cells, reducing intracellular ferrous iron and malondialdehyde, and balancing cellular redox status, thereby protecting cells from ferroptosis-like death. This study is the first to report\n                      <jats:italic toggle=\"yes\">Novosphingobium’s</jats:italic>\n                      dominance and persistence in a bacterial community during CIP stress in natural environmental conditions and to propose the stringent response-mediated ferroptosis-like death resistance as one of its key survival mechanisms.\n                    </jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE</jats:title>\n                      <jats:p>\n                        Antibiotics in the environment are increasingly recognized as a new class of pollutants that accelerate the evolutionary selection of antibiotic-resistant bacteria. However, little is known about how this selection occurs under natural conditions, including how specific bacteria taxa and mechanisms respond to particular antibiotics. This study reveals for the first time the selection effect of CIP on\n                        <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                        under nutrient-limited conditions, during which stringent response and iron homeostasis play important roles. An innovative linkage between stringent response and ferroptosis-like death resistance is proposed in\n                        <jats:italic toggle=\"yes\">N. pentaromativorans</jats:italic>\n                        US6-1, which serves as the CIP resistance mechanism for\n                        <jats:italic toggle=\"yes\">Novosphingobium</jats:italic>\n                        . These findings may help inform strategies to combat antimicrobial resistance in the natural environment.\n                      </jats:p>\n                    </jats:sec>\n                  </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40952106","pmcid":"PMC12542694","openalex_id":"https://openalex.org/W4414169352","authors":[],"funders":[{"funder_name":"MOST | NSFC | NSFC-Zhejiang Joint Fund | 浙江省科学技术厅 | Basic Public Welfare Research Program of Zhejiang Province","grant_id":"LTGS23C010002","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"21577121","title":null}],"total_grants":2,"fwci":0.8765,"citation_percentile":0.76671987,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1128/aem.01475-25","host_type":"journal"},{"url":"https://doi.org/10.1128/aem.01475-25","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/aem.01475-25","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40952106","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12542694","host_type":"repository"},{"url":"https://doaj.org/article/abf03d5f5669445faca8bd39c3d8112d","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12542694","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12542694?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Microbial Community Ecology and Physiology","Gut microbiota and health","Pharmaceutical and Antibiotic Environmental Impacts","Sphingomonadaceae","Anti-Bacterial Agents","Ciprofloxacin","Drug Resistance, Bacterial","Ferroptosis","Iron","Wetlands","Oxidative Stress"],"mesh_terms":["Ferroptosis","Anti-Bacterial Agents","Ciprofloxacin","Iron","Oxidative Stress","Drug Resistance, Bacterial","Sphingomonadaceae","Wetlands"],"keywords":["Siderophore","Oxidative stress","Bacteria","Stringent response","Antibiotic resistance","Dominance (genetics)","Persistence (discontinuity)","SOS response","Resistome","Novosphingobium","Ferroptosis-like Death"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"bioproject"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-14T13:22:12.921222Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}