Editorial: Global Dissemination and Evolution of Epidemic Multidrug-Resistant Gram-Negative Bacterial Pathogens: Surveillance, Diagnosis and Treatment, Volume III

João Pedro Rueda Furlan ^1* Raffaele Zarrilli ^2* Ziad Daoud ^3* Fang He ^4* Zhi Ruan ^5*

• ¹ Federal University of São Paulo, São Paulo, São Paulo, Brazil
• ² University of Naples Federico II, Naples, Campania, Italy
• ³ Central Michigan University, Mount Pleasant, Texas, United States
• ⁴ Hangzhou Medical College, Hangzhou, Zhejiang Province, China
• ⁵ Zhejiang University, Hangzhou, China

Aeromonas caviae were resistant to eleven antimicrobial agents but remained susceptible to ceftazidime. Several antimicrobial resistance genes (ARGs) and MGEs were detected by genomic analysis. Genomic islands were identified as harboring ARGs, which were related to class 1 integron and transposon. Chromosome-borne mcr-3.16 and mcr-3.3 (colistin resistance) were identified in A. veronii and A. caviae, respectively. These genes were flanked by insertion sequences. Furthermore, tandem regions and incomplete mcr-3-like genes were also observed.In vivo experiments classified A. veronii and A. caviae as moderately pathogenic and nonpathogenic, respectively.In hospitals from Southern Ethiopia, Odoko et al. examined the prevalence of species of Enterobacterales confer resistant to third-generation cephalosporins and carbapenems by the phenotypic detection of extended-spectrum β-lactamase (ESBL) and carbapenemases. The bacterial strains exhibited multidrug resistance, with Escherichia coli and Klebsiella pneumoniae were the most frequent. Accordantly, Enterobacteriaceae strains producing ESBL (66.6%, 46/69) and carbapenemases (21.7%, 15/69). Among patients suspected of surgical site, multidrug resistance rate of Enterobacteriaceae strains was 41% (25/61). By using multivariable analysis, it was identified that the length of hospital stay was a statistically significant factor associated with surgical site infection by ESBL-positive Enterobacteriaceae strains. These findings highlight the importance of ongoing phenotypic and genomic surveillance to track and understand MDR bacteria.Zhang et al. discussed the dissemination of genes encoding ESBLs in species from the Enterobacteriaceae family. Overall, ESBL-producing strains have been globally reported at the human-animal-environment interface, with blaCTX-M-15 gene being the most common ESBLencoding gene among all reservoirs. The environment was identified as a hotspot of cephalosporin-resistant and ESBL-producing bacteria. A great diversity of plasmid families has been identified as carrying these genes, highlighting IncF, IncI1, IncK, and IncN types. Among the insertion sequences and transposons related to ESBL-encoding genes, ISEcp1, IS26, IS903, IS1380, and Tn3, play a key role in the capture and mobilization of them. In this context, the need for continuous monitoring of ESBL-producing bacteria is considered desirable.In the food production chain, ESBL-positive strains have been constantly reported. In China, Bello et al. analyzed multidrug-resistant E. coli recovered from dairy cows. More than 20% of E. coli strains were multidrug-resistant. Genomic analysis revealed several ARGs, including blaCTX-M-55, mph(A), and qnrS1. Furthermore, MDR E. coli strains presented virulence factors associated with type III secretion system and adhesion. Phylogenetic analysis showed distinct evolutionary ST3579 and ST1121 lineages, suggesting that they originated from different ancestral populations. Besides, a pangenome analysis of diverse E. coli clones showed significant genetic diversity, with unique strain-specific genes found. MGEs were also identified, highlighting their role in bacterial diversity and adaptation.Accordingly, Liu et al. characterized ESBL-producing Salmonella strains from swine and broilers. S. Typhimurium and S. Enteritidis were the most prevalent serotypes in swine and broilers, respectively. The emergence of AMR was highlighted by the high percentage of multidrug resistance, which showed a downward trend over the period studied. Among the ESBL-positive Salmonella strains from swine, blaCTX-M-14 and blaCTX-M-65 were dominant and were harbored mainly by ST34 and ST17 clones. Poultry-derived Salmonella strains mainly harbored blaCTX-M-55 and blaCTX-M-65, which belonged to ST17 and ST198 clones. These findings emphasize the importance of monitoring MDR bacteria in the food production chain. Therefore, it is important to provide support for the effective prevention and control of antimicrobialresistant strains. .g.,. Colistin resistance associated with the mcr-1 gene and substitutions in MgrB was reported in Saudi Arabia and the UAE. Some high-risk clones of K. pneumoniae, including the ST11, ST307, and ST340, were identified in specific geographical regions. These findings highlight substantial gaps, particularly in community-based, environmental, and molecular epidemiology studies, while limited molecular and genome-based analyses hinder comprehensive AMR surveillance.Menezes et al. performed a prospective longitudinal study investigating the transfer of genes encoding broad-spectrum β-lactamases (i.e., ESBL, AmpC, and carbapenemase) of Enterobacteriaceae strains between companion animals and their cohabitant humans in Portugal and the United Kingdom (UK) during episodes of animal infection. Clinical specimens from dogs and cats, along with samples from their human cohabitants, were screened for antimicrobial-resistant strains, and whole-genome sequencing (WGS) was used to assess relatedness. ESBL/AmpC-producing strains were identified in companion animals and humans from Portugal and the UK, while carbapenemase-producing strains were detected in one dog from Portugal and another from the UK. Furthermore, transmission of index clinical E. coli and K. pneumoniae strains producing ESBL to cohabitant humans occurred in three Portuguese households, with repeated isolation of these strains in fecal samples from both animals and their owners. Besides, longitudinal sharing of E. coli strains between companion animals and their owners was identified in two households from Portugal and two from the UK. Interestingly, an MDR Enterobacter hormaechei subsp. hoffmannii strain was also shared within another Portuguese household.These findings underscore the household as a key epidemiological unit in AMR dissemination and highlight the need for targeted antimicrobial surveillance to inform and evaluate public health interventions.Convergence of hypervirulence and multidrug resistance poses a significant public health threat. In China, Zheng et al. conducted an active surveillance culture program from September 2020 to August 2021, screening 138 randomly selected pregnant women, with five undergoing sample collection at two different time points. A total of 41 carbapenem-resistant Acinetobacter baumannii (CRAB) strains were obtained and classified into four Cluster RS groups and one orphan pattern. Cluster RS 1, with eight complex types in pregnancy, was the dominant group globally, followed by Cluster RS 13, identified as hypervirulent KL49 CRAB with a strong geographical association to Guangdong, China. The maternal CRAB carriage rate was 26.09%, with half of the strains representing novel complex types, including CT3071, marking the first identification of KL7 strains in Shenzhen, China. Strains assigned as KL49 and KL7 were most frequently found in the same participant, suggesting intraspecific competition as a potential mechanism for CRAB infections occurring without prior colonization in pregnancy. Independent risk factors for CRAB carriage included advanced maternal age, gestational diabetes mellitus, and Group B Streptococcus infection. The high carriage rate and enhanced virulence of CRAB in pregnancy underscore the urgent need for routine surveillance to prevent dissemination within this high-risk group, particularly for Cluster RS 13 strains in Guangdong, China.(hvKp) strains belonging to K2-ST881 and K54-ST29 lineages in a single patient experiencing multiple-site infections during two independent episodes. All strains were highly susceptible to multiple antimicrobial agents. Plasmid analysis revealed that both virulence plasmids, pEDhvKp-1 and pEDhvKp-3, belonged to the IncFIB-type and carried several virulence genes.Currently and early strains were closely related. By using a mouse infection model, K2-ST881 and K54-ST29 strains demonstrated high virulence, causing more than 90% mortality within 72 hours post-infection. These findings expand the known diversity of hvKp lineages, reveal genomic adaptations associated with clonal switching between distinct hvKp strains in vivo, and highlight the urgent need for improved surveillance, diagnostic tools, and therapeutic strategies to address the threat posed by high-risk hvKp strains.In summary, the dissemination of MDR Gram-negative bacteria remains a critical public health challenge, driven by MGEs facilitating AMR across diverse environments. The presence of ESBL-and carbapenemase-producing strains at the human-animal-environmental interface highlights the urgent need for continuous surveillance and intervention strategies. The Guest Editors of this Research Topic hope these findings will inspire scientists to further explore and discuss the global spread and evolution of MDR Gram-negative bacterial pathogens.