Population structure-guided profiling of antibiotic resistance patterns in clinical<i>Listeria monocytogenes</i>isolates from Germany identifies<i>pbpB3</i>alleles associated with low levels of cephalosporin resistance

Fischer, Martin; Wamp, Sabrina; Fruth, Angelika; Allerberger, Franz; Flieger, Antje; Halbedel, Sven

doi:10.1101/2020.05.25.114330

Cited by 3 publications

(3 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inactivation of the class A PBPs had only mild effects on cephalosporin resistance in previous experiments (40), and were not further considered here. However, PBP B3, one out of three class B PBPs, substantially contributed to cephalosporine resistance (40, 41). Likewise, deletion of rodA1 and rodA2 only slightly affected cephalosporin resistance, whereas deletion of rodA3 had a greater impact (39).…”

Section: Resultsmentioning

confidence: 99%

“…In our current model, the PrkA→ReoM/ReoY→MurA/ClpCP→RodA3/PBP B3 cascade would represent a closed homeostatic circuit that senses lipid II (by PrkA) to control its production (through control of MurA stability) and consumption (by RodA3/PBP B3) (Fig 6). The genes in this pathway collectively determine the intrinsic resistance of L. monocytogenes to cephalosporins (24, 36, 39, 40, 50) and are conserved in several other Gram-positive bacteria (Fig S6) In Enterococcus faecalis , most of the corresponding homologues were shown to maintain the high intrinsic cephalosporin resistance level of this organism (29, 51–54), and deletion of pbpC , which encodes the PBP B3 homologue of B. subtilis (Fig S6), was also necessary for cephalosporin resistance (55). Moreover, inactivation of Stk1, the PASTA-eSTK of S. aureus , sensitizes methicillin resistant S. aureus (MRSA) against β-lactams including oxacillin and this is overcome by reoM and reoY deletions (28, 56).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MurA escape mutations uncouple peptidoglycan biosynthesis from PrkA signaling

Wamp

Rothe

Holland

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Gram-positive bacteria are protected by a thick mesh of peptidoglycan (PG) completely engulfing their cells. This PG network is the main component of the bacterial cell wall, it provides rigidity and acts as foundation for the attachment of other surface molecules. Biosynthesis of PG consumes a high amount of cellular resources and therefore requires careful adjustments to environmental conditions. An important switch in the control of PG biosynthesis of Listeria monocytogenes, a Gram-positive pathogen with a high infection fatality rate, is the serine/threonine protein kinase PrkA. A key substrate of this kinase is the small cytosolic protein ReoM. We have shown previously that ReoM phosphorylation regulates PG formation through control of MurA stability. MurA catalyzes the first step in PG biosynthesis and the current model suggests that phosphorylated ReoM prevents MurA degradation by the ClpCP protease. In contrast, conditions leading to ReoM dephosphorylation stimulate MurA degradation. How ReoM controls degradation of MurA and potential other substrates is not understood. Also, the individual contribution of the ~20 other known PrkA targets to PG biosynthesis regulation is unknown. We here present murA mutants which escape proteolytic degradation. The release of MurA from ClpCP-dependent proteolysis was able to constitutively activate PG biosynthesis and further enhances the intrinsic cephalosporin resistance of L. monocytogenes. This activation required the RodA3/PBP B3 transglycosylase/transpeptidase pair as additional effectors of the PrkA signaling route. One murA escape mutation not only fully rescued an otherwise non-viable prkA mutant during growth in batch culture and inside macrophages but also overcompensated cephalosporin hypersensitivity. Our data collectively indicate that the main purpose of PrkA-mediated signaling in L. monocytogenes is control of MurA stability during extra- and intracellular growth. These findings have important implications for the understanding of PG biosynthesis regulation and β-lactam resistance of L. monocytogenes and related Gram-positive bacteria.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MurA escape mutations uncouple peptidoglycan biosynthesis from PrkA signaling

Wamp

Rothe

Holland

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, a previous investigation discovered that none of the L. monocytogenes isolates recovered from milk samples have the ampC gene (Harshani et al, 2022). According to Meletis (2016), this may be related to mutations in «penicillin-binding proteins» (PBPs) that cause B-lactam resistance, contradicting other studies that claimed that the high percentage of ampicillin-resistant strains suggested amoxicillin/clavulanic acid as a better treatment option (Rezai et al, 2018;Fischer et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Molecular Detection of Listeria Species Isolated From Raw Milk with Special Reference to Virulence Determinants and Antimicrobial Resistance in Listeria monocytogenes

Mohamed¹,

K.G.²,

Al-Azeem³

et al. 2022

JAHP

View full text Add to dashboard Cite

Listeria monocytogenes is classified as a major foodborne pathogen associated with high mortalities due to severe invasive listeriosis, meningitis and abortion in humans. With particular emphasis on Listeria monocytogenes' capacity to form biofilms, antimicrobial resistance profile and virulence determinants, the purpose of this study is to discuss the presence of Listeria species in raw milk. In total, 150 samples of raw milk from vendors and nearby dairy farms in Sohag, Egypt, were collected. The samples underwent a bacteriological investigation. The results showed that 22 out of 150 samples had Listeria spp. contamination. Polymerase chain reaction (PCR) using the Listeria iap gene identified 13 of the 22 isolates that were reported as biochemically positive Listeria spp. Eight isolates of Listeria monocytogenes were molecularly confirmed, while the remaining five were subjected to 16S rRNA sequence analysis and identified as L. innocua (three isolates) and L. welshimeri (two isolates). The antibiotic susceptibility profiling revealed multidrug resistance of L. monocytogenes strains against several antimicrobials in addition, they harbored antibiotic resistance genes, including. ampC, aad6, tetM each present in 100% of our isolates and mefA (37.5%). Furthermore, different virulence genes, including the most often found virulence-associated genes hlyA and inlB (100% for each), inlA (50%) were present in our isolates. Interestingly, all of the isolates demonstrated varying degrees of biofilm forming capability. The pathogenicity of L. monocytogenes, particularly virulent, drug-resistant and biofilm-forming strains, is highlighted in this study and can result in a public health danger when present in raw milk. Therefore, it is essential to keep an eye on bacterial resistance in the setting of food production.

show abstract

Distribution of antimicrobial resistance among clinical and food Listeria monocytogenes isolated in Moscow in 2019–2021

Ermolaeva

Карпова

Andriyanov³

et al. 2022

CMAC

View full text Add to dashboard Cite

Objective. To determine the current state-of-art of acquired resistance to antimicrobial drugs among L. monocytogenes strains associated with listeriosis in humans and food contamination in Moscow. Materials and Methods. We used 39 L. monocytogenes strains isolated in Moscow in 2019–2021 from clinical material (n = 24) and food (n = 15). Resistance to 12 antibiotics of the first and second lines of defense was studied using disk-diffusion method. The parameters recommended for L. monocytogenes were used to interpret the results; in the absence of recommendations for L. monocytogenes, the criteria for Staphylococcus aureus and/or Enterococcus spp. were used. Results. All strains were susceptible to ampicillin, benzylpenicillin, erythromycin, vancomycin, imipenem, linezolid, and the amoxicillin/clavulanic acid. Resistance was observed to gentamicin (23%) as well as to meropenem, trimethoprim/sulfamethoxazole and ciprofloxacin (5%, 74% and 28% of strains, respectively). A total of 15 strains with multiple antibiotic resistance were identified (13 and 2 isolates were resistant to three and four antibiotics, respectively). Simultaneous resistance to trimethoprim/sulfamethoxazole, ciprofloxacin and levofloxacin was observed in 9 strains, 6 strains were resistant to gentamicin and trimethoprim/sulfamethoxazole, including 3 strains – to gentamicin, trimethoprim/sulfamethoxazole, levofloxacin, and 2 strains – to gentamicin, trimethoprim/sulfamethoxazole, ciprofloxacin. Comparison of the growth inhibition zones by ampicillin and benzylpenicillin in the studied strains with historical data on the strains isolated in Russia in 1950–1980 showed a significant downward shift in the size of growth inhibition zones. Comparison of the distribution of strains with different diameters of growth inhibition zones depending on the source of isolation did not show significant differences between clinical strains and strains of food origin isolated in 2019–2021. Conclusions. A wide spread of acquired resistance was shown among L. monocytogenes strains of clinical and food origin isolated in Moscow in 2019–2021. Despite the fact that all strains were susceptible to penicillins, the distribution of growth inhibition zone diameters showed a significant shift towards decreasing sensitivity to ampicillin and benzylpenicillin in strains isolated in 2019–2021 compared with L. monocytogenes strains isolated in Russia before 1980.

show abstract

Population structure-guided profiling of antibiotic resistance patterns in clinicalListeria monocytogenesisolates from Germany identifiespbpB3alleles associated with low levels of cephalosporin resistance

Cited by 3 publications

References 51 publications

MurA escape mutations uncouple peptidoglycan biosynthesis from PrkA signaling

MurA escape mutations uncouple peptidoglycan biosynthesis from PrkA signaling

Molecular Detection of Listeria Species Isolated From Raw Milk with Special Reference to Virulence Determinants and Antimicrobial Resistance in Listeria monocytogenes

Distribution of antimicrobial resistance among clinical and food Listeria monocytogenes isolated in Moscow in 2019–2021

Contact Info

Product

Resources

About