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Background <p>The alarming rise of antimicrobial resistance (AMR), especially in <i>Klebsiella pneumoniae</i>, demands urgent development of novel therapeutic strategies. Recently, probiotics and their metabolites, known as postbiotics, have gained attention due to their potential to enhance antibiotic efficacy and combat resistant pathogens. </p> Methods <p>In this study, 88 native <i>Lactobacillus</i> spp. isolates, were screened for antimicrobial activity against a highly resistant <i>K. pneumoniae</i> ATCC 7881 strain with a minimum inhibitory concentration ≥ 2048&#xa0;µg/mL. Based on screening results, four strains—<i>Lactiplantibacillus plantarum</i> RP155, 403, 225 and <i>Ligilactobacillus salivarius</i> RP317—were selected to produce postbiotics. Antimicrobial activity of these postbiotics, alone and combined with sub-inhibitory concentrations of amoxicillin and imipenem, was evaluated using the broth microdilution method. Gene expression of key antibiotic resistance determinants (<i>bla</i><sub>NDM</sub>, <i>bl</i>a<sub>CTX</sub>, <i>bla</i><sub>TEM</sub>, <i>bla</i><sub>SHV</sub>) was assessed by qRT-PCR following co-culture treatments.</p> Results <p>All postbiotics exhibited inhibitory effects on the growth of multidrug-resistant <i>K. pneumoniae</i> when applied in combination with low-dose antibiotics. Postbiotic concentrations ranging from 25 to 100&#xa0;mg/mL combined with 1–4&#xa0;µg/mL of amoxicillin or imipenem resulted in complete bacterial eradication. Molecular analyses revealed differential regulation of resistance genes: some postbiotics alone (notably <i>L. plantarum</i> RP225 and <i>L. salivarius</i> RP317) increased expression of specific resistance genes, whereas combinations with antibiotics significantly suppressed or completely silenced the expression levels of genes investigated.</p> Conclusion <p>Our findings demonstrate that native postbiotics, particularly in synergy with antibiotics, exert potent antimicrobial activity against multidrug-resistant <i>K. pneumoniae</i> and effectively downregulate critical resistance genes; highlighting the potential of postbiotics as adjunctive therapeutic agents in the battle against AMR.</p>

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Novel antimicrobial strategy: native postbiotics synergize with antibiotics to overcome resistance in Klebsiella pneumoniae

  • 期刊论文

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  • 发表日期：

    2025年11月10日

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  • Shadi Aghamohammad,
  • Fatemeh Sakaki,
  • Zahra Haghighatshenas,
  • Elham Haj Agha Gholizadeh Khiavi,
  • Farzad Badmasti,
  • Mahdi Rohani

摘要

Background

The alarming rise of antimicrobial resistance (AMR), especially in Klebsiella pneumoniae, demands urgent development of novel therapeutic strategies. Recently, probiotics and their metabolites, known as postbiotics, have gained attention due to their potential to enhance antibiotic efficacy and combat resistant pathogens.

Methods

In this study, 88 native Lactobacillus spp. isolates, were screened for antimicrobial activity against a highly resistant K. pneumoniae ATCC 7881 strain with a minimum inhibitory concentration ≥ 2048 µg/mL. Based on screening results, four strains—Lactiplantibacillus plantarum RP155, 403, 225 and Ligilactobacillus salivarius RP317—were selected to produce postbiotics. Antimicrobial activity of these postbiotics, alone and combined with sub-inhibitory concentrations of amoxicillin and imipenem, was evaluated using the broth microdilution method. Gene expression of key antibiotic resistance determinants (blaNDM, blaCTX, blaTEM, blaSHV) was assessed by qRT-PCR following co-culture treatments.

Results

All postbiotics exhibited inhibitory effects on the growth of multidrug-resistant K. pneumoniae when applied in combination with low-dose antibiotics. Postbiotic concentrations ranging from 25 to 100 mg/mL combined with 1–4 µg/mL of amoxicillin or imipenem resulted in complete bacterial eradication. Molecular analyses revealed differential regulation of resistance genes: some postbiotics alone (notably L. plantarum RP225 and L. salivarius RP317) increased expression of specific resistance genes, whereas combinations with antibiotics significantly suppressed or completely silenced the expression levels of genes investigated.

Conclusion

Our findings demonstrate that native postbiotics, particularly in synergy with antibiotics, exert potent antimicrobial activity against multidrug-resistant K. pneumoniae and effectively downregulate critical resistance genes; highlighting the potential of postbiotics as adjunctive therapeutic agents in the battle against AMR.